Hyperlipidemia is a metabolic disorder of lipids, it is a major risk factor of cardiovascular diseases and metabolic syndromes. This study aimed to synthesize a mutual prodrug of niacin with beta-sitosterol (compound 1a) and niacin with probucol (compound 1b) and obtain their antihyperlipidemic effectives and massive deleterious effects on cardiomyocyte on rats. A cross-sectional study was performed at Hawler Medical University/ in the Experimental Animal House of the College of Medicine /Erbil/Iraq, both mutual prodrugs were chemically synthesized through esterification reaction, seventy albino rats of both sex, were divided into 2 groups, control and treatment groups. The control group was subdivided into 2 subgroups (normolipidemic and hyperlipidemic subgroups) each consist of ten rats. While the treatment group was subdivided into 5 subgroups each contains ten rats (Niacin, beta-sitosterol, physical mixer of them, and the mutual prodrugs compound 1a and compound 1b), all along with high fat diet. Almost all compounds used in treatment group had a different degree of antihyperlipidemic effect, the mutual prodrug (compound 1a) showed the best results in lowering serum lipid levels also in modifying the deleterious effect on rat's cardio myocytes resulted from hyperlipidemia, while the mutual prodrug (compound 1b) showed non-promising effects. The synthesized mutual prodrug (Compound 1a) has appeared to be superior in lowering total cholesterol more than the physical mixture of niacin and beta-sitosterol, In addition to its ability to make the cardiac tissues returned near to normal.