Mango hoppers (Amritodus atkinsoni, Idioscopus niveosparsus and Idioscopus clypealis) are major pests affecting mango cultivation in Bhubaneswar, Odisha, where insecticide resistance has become a significant challenge. This study aimed to investigate the biochemical mechanisms of resistance, focusing on the activities of detoxifying enzymes Carboxylesterase (CE) and Glutathione-S-Transferase (GST). Seasonal variations in enzyme activity and kinetic properties (Km and Vmax) were analysed alongside bioassays to assess insecticide efficacy and the role of enzyme inhibitors. CE and GST activities were measured using established biochemical assays, while inhibitors such as Diethyl Maleate (DEM) and Triphenyl Phosphate (TPP) were tested for their ability to reduce enzyme-mediated resistance. Results showed that CE activity peaked at 1.89 µmol/min/mg in July 2023, a 5.3-fold increase from March 2022, while GST activity reached 297.43 µmol of CDNB conjugated/min/mg. These trends correlated with higher LC50 values for Acephate (4.442 ppm in October 2022, up from 1.471 ppm in March 2022) and Imidacloprid (1.313 ppm in July 2023, compared to 1.142 ppm in March 2022), indicating increased resistance. Kinetic analysis showed lower Km (11.33 µM for CE and 14.33 µM for GST in July 2023) and higher Vmax (1.32 µmol/min/mg for CE and 1.14 µmol/min/mg for GST), suggesting enhanced enzymatic efficiency. The use of DEM and TPP significantly reduced LC50 values, with DEM lowering LC50 by 45 % for Lambda-Cyhalothrin. These findings highlight the need for biochemical profiling and strategic enzyme inhibitor use to mitigate resistance. Seasonally tailored pest management strategies can enhance mango cultivation sustainability in Bhubaneswar.