Chemotherapeutic agents are in use for cancer, however, these agents showed severe side effects on vital organs upon treatment. This study aimed to evaluate the protective effect of the combinatorial treatment with Kaempferol (Kpf) and β-sitosterol (Bs) in hematological parameters and lipid profile alterations induced by cisplatin (Cis) toxicity in rats. Sixty male Sprague-Dawley rats were divided into five groups (N = 12). The first group (Gp1) served as a negative control. From Gp2 to Gp5, rats were fed on a high-fat diet (HFD) for 4 weeks, then Gp2 was injected with a single dose of Cis (7mg/kg B.Wt). Gp3, Gp4, and Gp5 were injected with Cis as in Gp2, then administered with Kpf (50mg/Kg B.Wt), Bs (50mg/Kg B.Wt) or Kpf /Bs as in Gp3, Gp4,  and Gp5, respectively. Blood samples were collected in heparinized and non-heparinized tubes for hematological and lipid profile investigations. The results showed that Cis treatment led to a significant decrease in the cellular compartments of blood and increased the mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). Cis treatment also caused an increase in the total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), atherogenic index (Risk 1), lipoprotein (a), and decrease the high-density lipoprotein (HDL-C). The treatment with a combination of Kpf/Bs after Cis ameliorated the above-mentioned hematological and lipid profile alterations.