Dichlorvos (DDVP) is an organophosphate insecticide that enhances food production and repels 25 disease vectors. However, it provokes cytotoxicity. 2S-hesperidin (2S-HES) is a potent 26 antioxidant, anti-inflammatory, and anti-lipidemic flavanone. Regardless, the 2S-HES impact on 27 DDVP-occupied hepatic injury remains fuzzy. We evaluated the therapeutic potential of 2S-HES 28 in a rat model of DDVP-elicited hepatic intoxication. Forty-two rats were randomly allotted to 29 seven groups (n=6/condition): control, DDVP (8 mg.kg⁻¹day⁻¹), DDVP with 2S-HES (50 and 30 100 mg.kg⁻¹day⁻¹), DDVP with atropine, and 2S-HES alone (50 and 100 mg.kg⁻¹day⁻¹). DDVP 31 was administered orally for 7 days, followed by 14 days of 2S-HES chemotherapy. 2S-HES 32 intervention partially mitigated DDVP-triggered alterations in leakage enzymes (ALT, AST, 33 ALP, LDH-5), total protein, albumin, globulin, bilirubin, electrolytes, ion-transporters, lipid 34 profiles, and HMG-CoA reductase. Furthermore, 2S-HES partially reversed DDVP-provoked 35 increases in hepatic H₂O₂, NO, and malondialdehyde; transposed DDVP-mediated decreased 36 liver GSH amount and activities of GST, SOD, catalase, and GPx; attenuated DDVP-triggered 37 upregulated NF-κB-p65 and caspase-3; and abated DDVP-engendered repressed interleukin-10 38 mRNA expression. Cytoarchitectural analyses authenticated the 2-HES reduction in DDVP-39 evoked hepatocellular vacuolation. Altogether, 2S-HES elicited promising alternative or 40 adjunctive therapy for partially mitigating DDVP-incited hepatic injury by attenuating leakage 41 enzymes, ionoregulatory disruptions, ion pump inhibition, dyslipidemias, oxidative stress, 42 inflammation, and apoptosis.