Non-traumatic osteonecrosis of the femoral head (NT-ONFH) is a common hip joint disease with a complex pathogenesis closely related to lipid metabolism disorders, oxidative stress, and alcohol toxicity. Acetaldehyde dehydrogenase 2 (ALDH2), a key enzyme in alcohol metabolism in humans, can lead to the accumulation of acetaldehyde or other aldehydes in the body due to reduced enzyme activity caused by gene mutations, which may further promote the occurrence and development of NT-ONFH. Studies have confirmed a significant association between ALDH2 gene polymorphisms and the onset of NT-ONFH. Individuals carrying mutant alleles (e.g., ALDH2*2) exhibit reduced alcohol metabolism capacity, making them more susceptible to microcirculatory dysfunction in the femoral head, osteoblast apoptosis, and abnormal differentiation of bone marrow mesenchymal stem cells, which accelerates the progression of osteonecrosis. This article systematically summarized the current research status on the impact of ALDH2 and its gene mutations on NT-ONFH, elucidated the underlying mechanisms at the cellular and animal experimental levels, and summarized factors related to disease progression as well as potential drugs and therapeutic targets identified in recent studies. Additionally, it analyzed the limitations and shortcomings of existing research and prospects future research directions, aiming to provide a theoretical basis for further revealing the pathogenesis of NT-ONFH and developing novel therapeutic strategies.