Aspartame (ASP) is one of the most widely used artificial sweeteners in the world. It is densely added to a large variety of food and drink. Parsley oil (PO) is one of the herbs widely used in recipes of folk medicine. PO has antioxidant, anti-inflammatory, and antiapoptotic activities. The present study investigated the protective effects of PO against hematotoxicity, nephrotoxicity and hepatotoxicity induced by ASP in a male albino rat. Thirty-two rats were divided into four groups. Control group: rats were given distilled water; PO group: rats were given orally PO daily (0.5 mL/kg b.wt.), ASP group: rats were given orally oral ASP daily (500 mg/kg b.wt.), and ASP combination with PO group: rats were given orally ASP combination with PO daily for 30 days. At the end of the experiment, blood, liver, and kidney samples were collected for hematological, biochemical, and histological studies. The results showed that ASP induced significant increase in mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), lymphocytes, monocytes, alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST), creatinine, urea, cholesterol, triglyceride, high density lipoprotein (HDL-c), and fasting blood glucose compared to control. While there is an insignificant change in red blood cells count (RBCs), hemoglobin (Hb), platelets count, white blood cells (WBCs) count, serum levels of uric acid in ASP versus control. The combination of ASP with PO showed significant decrease in MCHC, MCV, ALP, AST, ALT, creatinine, urea, cholesterol, triglyceride, HDL-c, and fasting blood glucose compared to ASP. The histological examination showed histopathological alterations in the liver tissue and renal tubules in the ASP group. In contrast, the liver and kidney tissues in ASP combination with the PO group appeared normal. In conclusion, PO protects liver, kidney, and blood from ASP toxicity in male rats. This protected effect may be due to pharmacological properties including antioxidant, hepatoprotective, neuroprotective, anti-diabetic activities of phenolic components in PO against ASP toxicity.