CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas (CRISPR associated endonuclease), a hotshot genome editing tool which is originally known to be the form of prokaryotic adaptive immune system against viral infections has gained all the attention of scientific community as a promising genome editing platform. This review encompasses a brief description of mitochondrial disease conditions associated with the alteration in mitochondrial genome (mtDNA) and highlights the key role of the CRISPR/Cas system pertaining to its working mechanism and its involvement in gene-based therapeutics in treating the foresaid mitochondrial diseases. Here, we also extend the perception related to the detailed mechanism of CRISPR/Cas system in mtDNA modification.