The world of One Piece is inhabited by powerful characters that possess extraordinary Devil Fruits. Monkey D. Luffy, the main protagonist, also falls into the same category. Luffy ate the Hito Hito no Mi, Model: Nika, a Mythical Zoan-type Devil Fruit, but its real name was erased as a means to hide its true power.
The Devil Fruit increases Luffy's physical abilities significantly, which explains how he can withstand so many blows. The Hito Hito no Mi, Model: Nika is definitely one of the most overpowered Devil Fruits in One Piece, but there are ways to counter it.
6 Haki
Haki is the easiest way to counter the effects of a Devil Fruit. A person can learn to use two types of Haki through training. These are Busoshoku Haki and Kenbunshoku Haki. Busoshoku Haki can be used to defend and attack a Devil Fruit user. If a person manages to master Busoshoku Haki, they can break through the toughest of defenses.
Haoshoku Haki, the third and rarest type of Haki, increases the damage output by a lot. Only a few characters are able to infuse Haoshoku Haki into their attacks, mainly because of how difficult it is. Kaido showed that Haki is the go-to counter against the power of the Hito Hito no Mi, Model: Nika.
5 ​​​​​​Yami Yami no Mi
The Yami Yami no Mi is among the most powerful Devil Fruits in the series. It was found by Thatch, but Blackbeard murdered him and ran away with it. Blackbeard was aware of the Devil Fruit's powers, so it didn't take long for him to gain control over it. Blackbeard used the Yami Yami no Mi to carve a path that led him to the position of an Emperor.
The Yami Yami no Mi allows Blackbeard to create and control darkness, which swallows everything in its path. The power of darkness is amplified by gravity; anything devoured ends up being completely crushed. The Yami Yami no Mi can also nullify the power of other Devil Fruits. In their brief confrontation in Impel Down, Blackbeard negated the effects of Luffy's Devil Fruit, which is how the former managed to hurt him.
4 ​​​​​​Biological Weapons
Some may find it hard to believe, but there are many biological weapons in One Piece that can take down the strongest of characters. Jack used Caesar's poison gas in Zou, which nearly destroyed the entire Mokomo Dukedom and made the job of the Beasts Pirates easy. In the Wano Country arc, Queen revealed two of his most lethal creations: the Mummy virus and the Ice Oni virus.
The Mummy virus is non-lethal; it causes severe fever and blood loss. It is also highly contagious and can spread in a short amount of time. The Ice Oni virus, on the other hand, is much more dangerous. Anyone infected with the virus sees an increase in their physical abilities, but they lose their senses. The infected people also gain the appearance of an Oni. The Ice Oni virus puts serious strain on the body of an individual, causing them to die within an hour. Before the might of these biological weapons, the Hito Hito no Mi, Model: Nika is useless.
3 ​​​​​​Seraphim
The Seraphim have been created by Dr. Vegapunk. The project was in the works before the Straw Hats even met Kuma, but it only reached its conclusion after the time skip. The process to create the Seraphim required extensive hard work and resources. Needless to say, the wait was worth it.
The Seraphim are equipped with Devil Fruits that suit their fighting style. They have Lunarian traits, which increase their physical abilities enormously. A single slash from S-Hawk's blade was enough to slice off a chunk of the mountain in Amazon Lily. The Seraphim have also shown that they can endure a tremendous amount of damage. Given their abilities, there is not much that Luffy and his Devil Fruit can do against them.
2 Ope Ope no Mi
The Ope Ope no Mi is a remarkable Devil Fruit that was eaten by Trafalgar Law. It falls into the Paramecia-type category, yet it is one of the most coveted Devil Fruits in the world. The Ope Ope no Mi allows Law to create ROOMs in which he can control everything.
Law can even bypass the effects of other Devil Fruits, which is a rare power. He can emulate the effect of Corazon's Nagi Nagi no Mi by creating a soundproof room. Furthermore, the Devil Fruit can even grant immortality to another person, although it comes at the cost of the user. If the Ope Ope no Mi were to fall into the hands of someone with better Haki, then they could easily counter all the powers of the Hito Hito no Mi, Model: Nika.
1 Characters With High Stamina
One of the biggest disadvantages of Luffy's Gear Fifth is its stamina consumption. The form drains Luffy's stamina quickly, so he has to be really careful while using it. Once Luffy is completely exhausted, it takes him a long time to recover and regain his normal form. While it gives Luffy an absurd amount of destructive power, he cannot fight in long battles.
If Luffy vs. Kaido had happened when both of them were well-rested, the latter would have won. Like the former Emperor, there are other characters who also have an ungodly amount of stamina, and they outlast Luffy. Although it may be a weakness at the moment, Luffy could overcome it in the future by training with his Devil Fruit.