A natural polymer, silk fibroin (Bombyx mori) was used as base anode material and was further modified by coating varied concentrations of Polydopamine for enriched MFC power generation. The performances of the modified anodes were compared to that of the base anode. The resultant anodes were all conductive, flexible, of 3D geometry with enriched macroporosity, biocompatibility and hydrophilicity. It was also observed that with an increase in the polymerization cycle the porosity of the anode has increased along with conductivity. A maximum bacterial colonization and power production was observed for the anode with the highest Polydopamine concentration (SFPDA-6) and lowest for the base (control). SFPDA-6 produced about 6x (56 mA/m2) more current density compared to that of the control (7 mA/m2). The predominant microbial colonies present in the anode and anolyte were analyzed by 16S rRNA sequencing and was found that the Bacillus dominated over the rest. The highest COD removal in the order of 84% was reported for SFPDA-6 anode. An analysis on cost estimation was carried out to reveal the commercial viability of the fabricated anodes for the large-scale MFC application and was found to be ∼$ 27.93 for SF anode and ∼$ 48.47 for SFPDA-6 with a working area of 15.71 cm2. Thus, the obtained results showed the potential of the Polydopamine modified silk fibroin anode as an effective anode material for real-time MFC operation.