Introduction: Azadirachta indica (Neem) is one of the widely used plants which has various medicinal properties like antipyretic, antimicrobial, antitumour, anti-inflammatory, antiulcer and antidiabetic effects. Silymarin-a milk thistle derivative has its own clinical significance. Sodium Benzoate (SB) is a versatile food preservative used in packaged food and drink industries which is consumed by the people unknowingly above World Health Organisation (WHO) standards which causes potential cytotoxicity. Aim: To evaluate the effect of Azadirachta indica leaf extract and the combination effect of Azadirachta indica leaf extract (Neem) with Silymarin against SB induced hepatorenal toxicity in adult male albino wistar rats. Materials and Methods: This experimental interventional animal study was conducted at Central Animal House at Aarupadai Veedu Medical College and Hospital, Puducherry, India from July 2021 to August 2021 for a period of 14 days. Total 30 male wistar rats were randomised into five groups with six rats into each group. The groups were Group 1 Control received only distilled water, Group 2 SB 200 mg/kg bw (SB) alone, Group 3 SB+Silymarin 100 mg/kg bw, Group 4 SB+ Azadirachta indica aqueous extract 400 mg/kg bw, Group 5 SB+Silymarin 100 mg/ kg bw+Azadirachta indica aqueous extract 400 mg/kg bw for 14 days through oral gavage. Doses and duration were determined based on previous studies. Blood was drawn from a retroorbital puncture, animals were sacrificed by euthanasia, a part of Liver and Kidney samples were sent for histopathological examination-cell structure, integrity, inflammation. Biochemical parameters of liver function tests-Serum Alanine Transaminase (ALT), Serum Aspartate aminotransferase (AST), Serum Alkaline Phosphatase (ALP) and Kidney function tests: urea, creatinine and uric acid were measured in serum. Statistical analysis were done by one-way Analysis of Variance (ANOVA) followed by Dunnet’s post-hoc test used for intergroup comparison, p-value <0.05 considered to be significant. Results: There was a significant increase in the activities of liver enzymes ALT, AST, ALP and kidney function (creatinine, uric acid) in the SB alone treated group when compared with the control group. Hepatorenal protection of Neem extract was shown by significant decrease in liver and renal parameters which was comparable to that of control and Silymarin standard drug. Combination of silymarin and neem showed significant protection in liver (ALT, AST, ALP) and kidney function (urea, creatinine, uric acid) when compared to neem alone treated group. All the results were substantiated by histopathological examination of liver and kidney tissues. Conclusion: This study suggests effect of Azadirachta indica leaf extract with Silymarin possess hepatorenoprotective effect against SB induced damage in rats. Combination effect of Azadirachta indica leaf extract with Silymarin significantly proved the hepatorenal protectivity when compared with Neem alone treated group.