Cancer-induced mortality is increasingly prevalent globally, which skyrocketed the necessity to discover new/novel, safe and effective anticancer drugs. Cancer is characterized by the continuous multiplication of cells in the human, which is unable to control. Scientific research is drawing its attention toward naturally-derived bioactive compounds as they have fewer side effects compared to the current synthetic drugs used for chemotherapy. Drugs isolated from natural sources and their role in the manipulation of epigenetic markers in cancer are discussed briefly in this review article. With advancing medicinal plant biotechnology and microbiology in the past century, several anticancer phytomedicines were developed. Modern pharmacopeia contains at least 25% herbal-based remedies, including clinically used anticancer drugs. These drugs mainly include the podophyllotoxin derivatives vinca alkaloids, curcumin, mistletoe plant extracts, taxanes, camptothecin, combretastatin, and colchicine artesunate, homoharringtonine, ellipticine, roscovitine, maytansine, tapsigargin,and bruceantin. Compounds (psammaplin, didemnin, dolastin, ecteinascidin, and halichondrin) isolated from marine sources and animals such as microalgae, cyanobacteria, heterotrophic bacteria, invertebrates. They have been evaluated for their anticancer activity on cells and experimental animal models and used chemotherapy.Drug-induced manipulation of epigenetic markers plays an important role in the treatment of cancer. The development of a new drug from isolated bioactive compounds of plant sources has been a feasible way to lower the toxicity and increase their effectiveness against cancer. Potential anticancer therapeutic leads obtained from various ethnomedicinal plants, foods, marine, and microorganisms are showing effective yet realistically safe pharmacological activity. This review will highlight important plant-based bioactive compounds like curcumin, stilbenes, terpenes, other polyphenolic phyto-compounds, and structurally related families that are used to prevent/ ameliorate cancer. However, a contribution from all possible fields of science is still a prerequisite for discovering safe and effective anticancer drugs.