The aim of this study is to determine the effects of l-asparaginase (l-ASP), corticosteroids (CSs), and antilipidemics, separately and in combination, on the lipid profiles and the liver and pancreas histology in mice. This study included 8 groups of 7 mice each. Before any drug administration, serum samples were taken from all of the mice. Then, normal saline was applied to the control group, and a medication or combination of medications was applied to the other groups. Levels of triglycerides, cholesterol (COL), and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) were determined, and the livers and pancreases were evaluated histologically at the end of the study. Triglycerides increased significantly in the CS-only and the l-ASP-only groups, COL increased significantly in the CS-only group, and HDL increased significantly in the CS-only and the antilipidemic-only groups. LDL was significantly lower in the CS-only and the l-ASP-only groups. CSs and l-ASP were significantly effective in liver necrosis, l-ASP was significantly effective in liver balloon degeneration, and CS were significantly effective in pancreas vacuolization. Triglyceride measurement is recommended before/during CS and/or l-ASP treatment. Starting with an antilipidemic agent can be considered to avoid possible complications in patients with significantly high rates. Indicators of a possible liver or pancreas injury should also be considered.