Keloid is a common skin disease, and the mechanism of its occurrence is not fully understood. There is evidence to show that multiple factors such as genetics, race, age, gender, hormones, infection, immunity, and oxidative stress, etc. may be related to the occurrence of keloids. Metabolic remodeling and protein acylation modification, as two important biological processes, play important roles in various skin related diseases. Based on this, this article reviews the roles of metabolic remodeling and protein acylation modification in keloids and the interrelationship between the two biological processes, and explores the application prospects of targeting the two biological processes in the prevention and treatment of keloids.