Our study aimed to assess the efficiency of Curcumin nanoformulation (LCC) on experimental nephrotoxicity induced by Gentamicin in rats. Six groups of seven rats were used: C-(control group) received saline solution i.p. (i.p. = intraperitoneal), G-gentamicin (G, 80 mg/kg body weight (b.w.)), GCC1 and GCC2-with G and CC solution (single dose of 10 mg/kg b.w.-CC1, or 20 mg/kg b.w.-CC2), GLCC1 (10 mg/kg b.w.) and GLCC2 (20 mg/kg b.w.) with G and LCC administration. Oxidative stress parameters (NOx = nitric oxide, MDA = malondialdehyde, TOS = total oxidative stress), antioxidant parameters (CAT = catalase, TAC = total antioxidant capacity), matrix metalloproteinases (MMP-2 and MMP-9), and renal function parameters (creatinine, blood urea nitrogen, and urea) were measured. Kidneys histopathologic examination was made for each group. Pretreatment with CC and LCC in both doses had significantly alleviating effects on assessed parameters (NOx, MDA, TOS, CAT, TAC, MMP-2, and -9) as compared with the untreated group ( < 0.006). Histopathological aspect and renal function were significantly improved in CC and LCC groups. Liposomal formulation (LCC) showed higher efficiency on all examined parameters compared to CC ( < 0.006). Our results demonstrated improving renal function and kidney cytoarchitecture, oxidative stress/antioxidant/balance, and MMPs plasma concentrations with better dose-related efficacity of LCC than CC.