The cytochrome P450 (CYP) is a large and complex eukaryotic gene superfamily with enzymatic activities involved in several physiological and regulatory processes. As an objective, an in-silico genome-wide DNA methylation (5mC) analysis was performed in rice (Oryza sativa cv. Zhonghua11), and the epigenetic role of CYPs in two abiotic stresses was observed. Being a stable representative mark, DNA-methylation alters the gene expression under stressful environmental conditions. Rice plants under salinity and drought stresses were analyzed through MeDIP-chip hybridization, and 14 unique genes of the CYP family were identified in the rice genome with varying degrees of methylation. The gene structure, promoter sequences, and phylogenetic analysis were performed. Furthermore, the responses of CYPs to various abiotic stresses, including salinity, drought, and cold were revealed. Similarly, the expression profile of potential CYPs was also investigated under various phytohormone stresses, which revealed the potential involvement of CYPs to hormone regulations. Overall, the current study provides evidence for CYP’s stress regulation and fundamental for further characterization and understanding their epigenetic roles in gene expression regulation and environmental stress regulation in higher plants.