This experiment was conducted to evaluate the effect of milk thistle (Silybum marianum) seed powder supplementation in the diet on weight gain, feed conversion efficiency, and physiological parameters in fattening lambs. In this experiment, thirty crossbred Shawl × Romanov male lambs were divided into three groups based on a completely randomized design. The experimental treatments included a control group receiving a diet without milk thistle seed powder (MSP), a group receiving a diet containing 1 % MSP, and a group receiving a diet containing 2 % MSP. Animals fed the diet containing 2 % MSP exhibited higher nutrient intake, average daily gain, and final body weight compared to the other treatment groups (P < 0.05). Lambs receiving the 2 % MSP diet had the most favorable feed conversion ratio (P < 0.05). The apparent digestibility of dry matter, organic matter, and crude protein was highest in lambs fed the diet containing MSP compared to the control group (P < 0.05). Ruminal NH3-N concentration and populations of total protozoa and Entodinium genus were lowest in lambs fed the MSP-containing diets (P < 0.05). The molar concentrations of acetate and valerate in the rumen fluid of lambs receiving the diet containing 2 % MSP were lower compared to the control group, while propionate concentration was higher (P < 0.05). Feeding the diet containing 2 % MSP reduced serum cholesterol, triglycerides, LDL, and liver enzyme activities compared to the control group (P < 0.05). Based on these results, supplementing lamb diets with 2 % MSP increased growth performance measures, nutrient digestibility coefficients, and reduced blood cholesterol and LDL concentrations.