Introduction <p>Silymarin is an extract of the plant Silybum marianum, which is used as a complementary treatment for liver diseases. However, it significantly interferes with lipid metabolism, and also affects glucose metabolism—in animal models, its administration led to a significant rise in plasma glutathione, while in in vivo models it decreased podocyte damage with nephroprotection in diabetic nephropathy.</p> Material and methodology <p>We performed a pilot, monocentric, analysis of patients transplanted at the Transplantation-Nephrology Department of UNM in patients with insulin resistance defined by HOMA-IR index &gt; 2 with subsequent supplementation of 450&#xa0;mg of silymarin per day for 180&#xa0;days with monitoring of metabolic parameters, graft function and level immunosuppressants.</p> Results <p>Our study was a prospective study including 28 patients after primary kidney transplantation, 71.4% men (<i>n</i> = 21). The average age of patients at the time of initiation of silymarin supplementation was 52.6 ± 10.2&#xa0;years, 42.8% of patients (<i>n</i> = 12) had a glucose metabolism disorder. We did not observe statistically significant changes in the monitored parameters during the silymarin supplementation in the time horizon of three and six months. We did not observe statistically significant differences in the observed parameters in the group of patients without a disorder of carbohydrate metabolism. In patients with impaired glucose tolerance or non-insulin-dependent diabetes mellitus, we recorded a statistically significant decrease in LDL-cholesterol during the observed period (<i>P</i> = 0.0170).</p> Conclusion <p>In our study, we did not confirm a significant effect of silymarin supplementation on insulin resistance and carbohydrate metabolism, graft function, but the effect on lipid metabolism and reduction of plasma LDL-cholesterol concentrations in patients with diabetes mellitus or prediabetes may be promising.</p>