Genetic mutation, vitamin and folate deficiencies, diet high-calorie and renal impairment could induce homocysteine (Hcy) -associated metabolic disorders in multiple tissues (liver, kidney, etc.) and lead to increased plasma Hcy levels, finally resulting in hyperhomocysteinemia (HHcy). HHcy is closely related to the occurrence and development of various diseases. However, the underlying mechanisms are complex and poorly understood. This article reviews the relationship between Hcy metabolism and related diseases, discusses the latest advances in the mechanism underlying the disorders of Hcy metabolism, as well as the current state of disease treatment, further providing possible intervention strategies for the treatment of HHcy -associated diseases.