Dioxins are compounds classified as persistent organic pollutants, from which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic to living organisms. TCDD is considered a carcinogen and has proinflammatory influence on animals and humans, promoting free radicals' formation, and binding with the aryl hydrocarbon receptor (AhR) leads to expression of cytochrome p-450 genes that in turn predisposes to mutations. Natural flavonoids, in this case xanthohumol (XN), have been reported to attenuate TCDD toxicity through inhibition of the transformation of the AhR. Moreover, XN shows antioxidant properties. The aim of the study was to compare the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and XN on lipid, liver enzyme, estradiol, and thyroid enzyme levels in the serum of Japanese quails. Adult, six-month-old, Japanese quails were divided into eight groups according to treatment procedures. Serum levels of total cholesterol (TCh), high-density lipoproteins (HDLs), triglycerides (TGs), estradiol, triiodothyronine, and thyroxine, and activities of alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase were measured. In comparison with the control group, 2,3,7,8-tetrachlorodibenzo-p-dioxin significantly decreased concentrations of serum HDLs and thyroid hormones and significantly increased the serum TCh level. Levels of serum TGs, liver enzymes, and estradiol were not changed after 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment. Based on our data, XN treatment may also increase the levels of thyroid hormones. Moreover, the tested dioxin disrupts the liver function, especially changing lipids' metabolism. Therefore, more studies are needed for better understanding the mechanism of toxic influence of 2,3,7,8-tetrachlorodibenzo-p-dioxin on key metabolic pathways and organs in living organisms.