Crocodile, a former Great Pirate, possesses the Sand-Sand Fruit – a Logia that enables him to create and transform into sand. Like other Logia users, most physical attacks would pass through him without effect. However, water and blood render the sand hard, which Luffy used to counter Crocodile before mastering Haki.
What is terrifying about Crocodile’s power is his ability to absorb all moisture from an object by touching it. He used this skill on Luffy, who would have been mummified and died if not for external intervention. Even with Gear 5, Crocodile could render Luffy’s transformation useless if he manages to mummify him.
Sugar, a member of the Donquixote Pirates, consumed the Toy-Toy Fruit, a Paramecia that allows her to transform anyone into a living toy. This Devil Fruit also halts aging, hence her appearance as a young girl.
Theoretically, even if Luffy uses Gear 5, he can be transformed into a toy by Sugar. If Sugar establishes a contract with Luffy, he would have to obey all her orders. The only solution for Luffy would be if Sugar loses consciousness.
Luffy and Trafalgar D. Water Law were allies, but in a true battle, Law could counter Gear 5. He possesses the power of the Op-Op Fruit, which allows him to manipulate space within a delimited sphere.
Even if Luffy uses Gear 5, Law could effortlessly cut him into several pieces with a simple swing of his sword. These cuts could occur without even physically touching the opponent. If this were to happen, Luffy would be immobilized.
As Kaido mentioned, sharp attacks can harm Luffy even in Gear 5. Zala, from Baroque Works, consumed the Spike-Spike Fruit. She can sprout spikes from her body. If someone more powerful possessed this ability, they could impale Luffy.
Inazuma, Emporio Ivankov’s right-hand, ate the Scissor-Scissor Fruit, allowing him to transform his body into scissors. He can cut through anything like paper. By using his scissors, Inazuma could wound Luffy, complicating the elasticity of the Straw Hat captain. However, Inazuma alone is not very threatening.
Jewelry Bonney, the only female member of the Worst Generation, has a Devil Fruit that allows her to manipulate age. On Egghead Island, she aged Luffy by 70 years, rendering him too weak to move. Even in Gear 5, he may not be able to withstand it if she ages him too much.
Charlotte Mont-d’Or, the 30th child of Charlotte Linlin, possesses the Book-Book Fruit, which enables her to manipulate books. She could trap Gear 5 Luffy in a book, leaving the Straw Hat captain helpless. The element of surprise would be the greatest threat.
Kuma, a Revolutionary turned Great Pirate, has the Paw-Paw Fruit. His palms can repel anything they touch. Even Gear 5 would not be able to counter this defense. Luffy would not even be able to touch Kuma.
Daz Bonez, from Baroque Works, could literally cut Luffy into pieces in Gear 5. He possesses the Blade-Blade Fruit, which transforms his body into steel blades. A formidable opponent for Luffy if it were in the hands of a more skilled character. But we have no doubt about Luffy’s ability to adapt to the situation!
The Dark-Dark Fruit, consumed by Teach, allows him to manipulate darkness. Even if Luffy can reach him, Teach can negate any Devil Fruit power. Thus, he could nullify Luffy’s transformation at any moment.
The world of One Piece is filled with potential adversaries for Luffy, even in Gear 5. But his determination may well enable him to overcome these challenges.