As per World Health Organization cancer remains as a leading killer disease causing nearly 10 million deaths in 2020. Since the burden of cancer increases worldwide, warranting an urgent search for anti-cancer compounds from natural sources. Secondary metabolites from plants, marine organisms exhibit a novel chemical and structural diversity holding a great promise as therapeutics in cancer treatment. These natural metabolites target only the cancer cells and the normal healthy cells are left unharmed. In the emerging trends of cancer treatment, the natural bioactive compounds have long become a part of cancer chemotherapy. In this review, we have tried to compile about eight bioactive compounds from plant origin viz. combretastatin, ginsenoside, lycopene, quercetin, resveratrol, silymarin, sulforaphane and withaferin A, four marine-derived compounds viz. bryostatins, dolastatins, eribulin, plitidepsin and three microorganisms viz. Clostridium, Mycobacterium bovis and Streptococcus pyogenes with their well-established anticancer potential, mechanism of action and clinical establishments are presented.