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The prevalence of cancer and diabetes has been a major global threat that has led to the continuous investigation of numerous biomarker that can serve in novel therapeutic targets for their treatment. Recently, epigenetic regulatory function of EZH2-PPAR was discovered to influence the metabolic and signaling pathway causing this disease. Hence, the synergistic combination of inhibitors like GSK126 and Bezafibrate was reported have promising outcome for these disease treatment, but without clear understanding of other biomarker association and side effect detriment. The disease association and protein interaction networks between EZH2-PPARs and other biomarkers regulating pancreatic cancer and diabetes pathology were identified, with obesity, and hypertensive disease being the closest vast connection. Natural compounds employed in the molecular docking, adme/toxicity and reactivity screening for candidate inhibitor of versatile capacity against the target identify nine compounds as lead hits. Overall, Phytocassane A exhibit the most recognizable insilico validation for drug likeness profiles better than the standards, and all nine compounds were conclusively proposed for further experimental screening to compliment this finding on their benefit in drug development for diabetes and cancer therapy.