Firstly, a graphene-MoS2/POPD modified glassy carbon electrode was fabricated from hydrothermally prepared graphene-MoS2 hybrid, and electrochemically prepared POPD. The graphene-MoS2/POPD modified electrode catalyzes H2S oxidation at a minimized overpotential (+ 0.15 V vs. Ag/AgCl), and led to establish an ultrasensitive H2S detection platform. It can detect 0.1 nM concentration of H2S under complex biological conditions. Our experimental results indicates the synergic properties of two excellent 2D materials, graphene and MoS2 provides signal amplifications. Moreover, POPD provides high selectivity to the interface, eliminating up to 2.5-fold surplus levels of biological interferences, and providing 98.5% anti-fouling capacity. Secondly, POPD/MoS2/ZnCo2O4 modified carbon cloth electrode was developed via hydrothermal growth of ZnCo2O4 and MoS2 followed by electrodeposition of POPD. The resulting sensor showed excellent sensing aptitude to H2S, because of its rich redox chemistry and extended electrocatalytic sites. The repulsive forces between sulfur layers of MoS2 and elemental sulfur of H2S-oxidized product is used to alleviate sulfur passivation and to maintain a reproducible electrode surface. Using amperometric technique, both the electrodes have shown appreciable practical feasibility in human blood, serum, and urine samples at physiological pH. They were able to track real-time quantitative productions endogenous H2S in e. coli. Future work is directed towards employing these sensors in monitoring H2S drug release kinetics and transport in cancer cells.