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The purpose of this study was to investigate the effects of Tongmai granule residue (TGR) on the growth performance, apparent nutrient digestibility, blood biochemical parameters, and rumen fermentation in Doper x Small Tail Han hybrid sheep. Twenty-four healthy female lambs (6–7 months of age; 29.64 ± 1.80 kg initial body weight) were randomly divided into 3 groups and fed for 75 days. The control group was fed a commercial concentrate and the other groups were fed diets supplemented with 10% and 15% TGR respectively. Dietary 15% TGR supplementation decreased average daily gain, apparent digestibility of neutral detergent fiber, but increased the feed conversion ratio, apparent digestibility of crude fat and organic matter in lambs (P < 0.05). The 10% TGR group significantly increased the apparent digestibility of organic matter (P < 0.05). Dietary supplementation of 10% and 15% TGR significantly increased serum high density lipoprotein cholesterol (HDL-C) content on day 15, IgG content on day 30, and IgA content on day 60 of the feeding period (P < 0.05). Dietary supplementation of 15% TGR significantly increased the content of IgA on the 30th day (P < 0.05), and significantly decreased blood urea nitrogen (BUN) on the 30th day (P < 0.05) of the feeding period. TGR at 15% significantly decreased the contents of acetic acid, propionic acid, butyric acid, and total volatile fatty acids (TVFA) in the rumen (P < 0.05), and significantly increased the pH, NH3-N concentration, and acetic acid: propionic acid ratio (P < 0.05). The results suggest that, the addition of TGR to diet can improve the apparent digestibility of crude fat and organic matter, and improve the anti-atherosclerosis ability and immune function of Doper x Small Tail Han hybrid female lambs. The dietary addition of 10% TGR yielded the best feeding effect in this experiment.