This study aims to fill this critical gap by: (1) examining the impact of Mitochondria-derived peptides (MDPs), such as Humanin, MOTS-c, and p66Shc, together with ACE genotypes in the context of cardiovascular disease (CVD), hypertension (HT), and diabetes mellitus (DM); (2) clarifying the intricate interplay between these mitochondrial factors and the progression of depressive disorders, and advance understanding of the role of mitochondrial-derived oxidative stress peptides in the progression of depressive disorders. The gene discussed is ACE; the disease is diabetes mellitus.