Herein, a cancer-specific dopamine-conjugated sp 2 -rich carbonized polymer dot (PD)-encapsulated mesoporous MnO 2 (MnO 2 @PD)-mineralized hydrogel biosensor was developed that offers cancer-induced observable in situ alterations in fluorescence (FL), electrochemical, and mechanophysical properties. Cancer-triggered MnO 2 degradation in the hydrogel, prompted by increased levels of glutathione (GSH) and reactive oxygen species (ROS) such as H 2 O 2 , leads to PD release and FL restoration, thereby controlling changes in the pore structure and increasing hydrogen bonding, resulting in physiologically visible alterations in mechanical stretchability, viscosity, swelling behavior, and adhesiveness. The pore size of the matrix increased from 21.83 to 36.81 m 2 /g upon GSH treatment, affecting the viscosity and swellability of the system. The resistance increased from 21.96 ± 1.16 to 30.69 ± 2.01 and 32.21 ± 2.54 kΩ, respectively, confirming the dependence of conductivity changes on H 2 O 2 and GSH treatments. The in vitro treatment with cancer cells (HeLa, PC-3, and B16F10) facilitated a tunable electrochemical sensing performance via redox-mediated MnO 2 breakdown by intracellular ROS and GSH, whereas hydrogels treated with normal cells (CHO-K1) showed minimal changes. Cancer-microenvironment-derived water-drop sensing showed three times higher response as compared to the normal cell-treated hydrogel. The sensing capability of the fabricated sensor was validated based on bending-induced relative resistance changes under dry and wet conditions. Moreover, the integration of the developed sensor with a wireless sensor enabled real-time monitoring with a smartphone.