Background: Brassica nigra possesses a significant concentration of bioactive compounds and has been demonstrated to have a variety of pharmacological properties, although its sprout has not been extensively studied. Thus, the protective effects of Brassica nigra sprout hydroalcoholic extract (BNSE) on lipid homeostasis, hepatotoxicity, and nephrotoxicity in cyclophosphamide (CYP)-induced toxicity in rats were examined in this study. Methods: Four experimental rat groups (n = 8 for each group) were examined as follows: NR, normal rats that received normal saline by oral gavage daily; CYP, injected with a single dose of CYP at 250 mg kg−1 intraperitoneally (i.p.) and did not receive any treatment, receiving only normal saline by oral gavage daily; CYP + BNSE250, injected with a single dose of CYP at 250 mg kg−1 i.p. and treated with BNSE at 250 mg kg−1 by oral gavage daily for three weeks; and CYP + BNSE500, injected with a single dose of CYP at 250 mg kg−1 i.p. and treated with BNSE at 500 mg kg−1 by oral gavage daily for three weeks. Results: The results indicated a significant increase (p < 0.05) in triglyceride (TG), cholesterol (CHO), low-density lipoprotein cholesterol (LDL-c), and very low-density lipoprotein cholesterol (VLDL-c) levels in CYP-induced toxicity rats. The administration of BNSE at 250 and 500 mg kg−1 significantly (p < 0.05) attenuated TG, CHO, LDL-c, and VLDL-c at values comparable with the NR group. The most efficient treatment for improving the lipid profile and atherogenicity complication was BNSE at 500 mg kg−1, performing even better than 250 mg kg−1. Administrating BNSE at 250 or 500 mg kg−1 improved the liver’s function in a dose-dependent manner. Comparing the lower dose of 250 mg kg−1 of BNSE with 500 mg kg−1 showed that administrating 250 mg kg−1 attenuated alanine transaminase (ALT) by 28.92%, against 33.36% when 500 mg kg−1 was given. A similar trend was observed in aspartate aminotransferase (AST), where 19.44% was recorded for BNSE at 250 mg kg−1 and 34.93% for BNSE at 500 mg kg−1. Higher efficiency was noticed for BNSE at 250 and 500 mg kg−1 regarding alkaline phosphatase (ALP). An improvement of 38.73% for BNSE at 500 mg kg−1 was shown. The best treatment was BNSE at 500 mg kg−1, as it markedly improved liver function, such as total bilirubin (T.B.), in a dose-dependent manner. The administration of BNSE attenuated the total protein (T.P.), albumin, and globulin levels to be close to or higher than the typical values in NR rats. Conclusions: BNSE might be used for its promising hypolipidemic, hepatoprotective, and nephroprotective potential and to prevent diseases related to oxidative stress. Further research on its application in humans is highly recommended.