Malathion-induced renal impairment and the protective agents against it; are still points of research. The current study aimed at investigating and comparing between L-carnitine (LC) (100 mg/kg/day) and Erdosteine (Er) (10 mg/kg/day) regarding their protective effects against subacute nephrotoxicity of low dose Malathion (M27) (27 mg/kg/day) as well as high dose Malathion (M54) (54 mg/kg/day). Ten equal groups of adult male Sprague Dawley rats (n=6) were used as the following: Control, Corn oil, (M27), (M54), (LC), (LC+M27), (LC+M54), (Er), (Er+M27) and (Er+M54). Rats received treatments by oral gavage for 28 days. Malathion showed significant dose dependent elevation of serum creatinine, urea and renal malondialdehyde, in line with decreasing serum albumin, renal superoxide dismutase activity and renal reduced Glutathione concentration. Histologically, Malathion induced marked degenerative and inflammatory changes as well as significant dose dependent increase in Caspase-3 expression in both renal cortex and medulla compared to control. Co-administration of either LC or Er with Malathion; was associated with significant improvement of renal biochemical functions, renal oxidative stress markers, histological degenerative as well as inflammatory changes and Caspase-3 expression in both low dose and high dose Malathion groups. Moreover, LC nephroprotective effects appeared to be better than those of Er, although these differences were statistically insignificant. To conclude, it was the first time to demonstrate the nephroprotective effects of LC and Er against Malathion-induced renal dysfunction; yet the upper hand was to LC.