Hydrogen sulfide (H₂S) is one of the three known gas signal transducers, and since its potential physiological role was reported, the literature on H₂S has been increasing. H₂S is involved in processes such as vasodilation, neurotransmission, angiogenesis, inflammation, and the prevention of ischemia-reperfusion injury, and its mechanism remains to be further studied. At present, the role of post-translational processing of proteins has been considered as a possible mechanism for the involvement of H₂S in a variety of physiological processes. Current studies have shown that H₂S is involved in S-sulfhydration, phosphorylation, and S-nitrosylation of proteins, etc. This paper focuses on the effects of protein modification involving H₂S on physiological and pathological processes, looking forward to providing guidance for subsequent research.