The prominence of side effects or adverse reactions due to the existing drugs and polymers paved a need for the researchers to explore and investigate dietary substances and natural raw materials for therapeutic benefits. The current research was focused to fabricate and optimize layered colon targeted tablet of curcumin using natural excipients. Layered tablet was formulated using mucoadhesive polymers and enteric coating polymers. Compression coating technique was used to incorporate mucoadhesive polymers and dip coating technique was used for incorporating enteric polymers on curcumin loaded core tablets. Natural sources like Abelmoscus esculentus fruits, Hibiscus rosa-sinensis leaves, Artocarpus heterophyllus fruit, Linum usitatissimum seeds and Colocasia esculenta corms were used for extraction of mucoadhesive polymers. Natural ingredients like Starch, Pectin, Inulin and shellac were used as enteric coating polymers. Invitro dissolution studies for the optimized formulation was conducted using simulated dissolution media of pH 1.2 for first 2 h, pH 4.5 for further 2 h, pH 7.4 for another 2 h. The formulation containing 30% pectin, 10% shellac and 20% linum seed gum was found to reach the colorectal region with expected drug release. Thus, it’s concluded that the optimized formulation makes a potential biodegradable colon targeted formulation for treating colorectal cancer, ulcerative colitis etc.