Increased levels of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy), is an independent risk factor of various diseases. Clinical studies report that people born with severe HHcy develop skeletal malformations with weaker bone. Studies also report that altered mitochondrial dynamics and altered epigenetics contribute to weaker bones and bone diseases. Although Hcy-induced mitochondrial dysfunction has been shown to affect bone metabolism, the role of mitochondrial epigenetics (mito-epigenetics) has not been studied in bones. The epigenetics in mitochondria is interesting as the mitochondrial genome size is small (16 kb) with fewer CpG, and without histones and introns. Recently, fascinating works on epigenetics along with the discovery of histone-like proteins in mitochondria are giving exciting areas for novel studies on mitochondria epigenetics. There are mutual cause and effect relationships between bone, mitochondria, Hcy, and epigenetics, but unfortunately, studies are lacking that describe the involvement of all these together in bone disease progression. This review describes the reciprocal relationships and mechanisms of Hcy-bone-mitochondria-epigenetics along with a short discussion of techniques which could be employed to assess Hcy-induced anomaly in bone, mediated through alterations in mito-epigenetics.