The current research work aimed to evaluate some physiological effects of honey on cholesterol and triglycerides in albino mice by studying some of its physical-chemical characteristics and biological activities. Four groups of mice were fed with four honey varieties (nigella, moringa, sidr, and pumpkin honey), at the rate of 1 mL honey/10 mL water. The results depicted that moringa honey reported the highest moisture content 18.55% followed by Nigella sativa honey 18.11%, while pumpkin honey reported the lowest value 17.02%. The protein content of honey varieties varied from 4.99% (pumpkin honey) to 9.11% (sidr honey), and the pumpkin honey and sidr honey had the same ash value of 0.75%. The fat content of honey varieties varied from 0.09% (sidr honey) to 0.22% (pumpkin honey). The fiber content of honey varieties varied from 1.79% (sidr honey) to 2.13% (moringa honey). The carbohydrate content of sidr band moringa honey was 70.93% and 74.92% respectively. The honey acidity content followed this declining pattern, pumpkin (4.52%) sidr (4.17%), and nigella (4.06%). Regarding the total soluble solids content, the values were 81.15°Brix, 79.71°Brix, and 77.11°Brix for the pumpkin, moringa and Nigella sativa honey, respectively. The honey density ranged from 1.39 kg/L to 1.41 kg/L. It was noted that the highest (25.77 mm) and lowest (24.12 mm) inhibitions zones for Escherichia coli, were recorded by moringa honey and pumpkin honey respectively. Likewise, the maximum (28.77 mm) and minimum (24.12 mm) Salmonella enteritidis inhibition was recorded in the moringa and sidr honey respectively; while the zone of inhibitions of Bacillus cereus values varied from 7.45 mm (sidr honey) to 12.75 mm (pumpkin honey). Furthermore, the greatest values for the very low-density Lipoprotein (VLDL) (0.84 mmol/L) and triglyceride (TG) (0.92 mmol/L) were detected in the mice fed with moringa honey; and the highest high-density lipoprotein value (HDL) (1.22 mmol/L) was detected in the mice fed with pumpkin honey. In contrast, the control mice developed the highest values in low-density lipoprotein (LDL) (2.57 mmol/L) and total cholesterol (TC) (2.66 mmol/L); while the mice fed with Nigella sativa honey and pumpkin honey reported the lowest value of LDL and TC values of 0.62 mmol/L and 0.62 mmol/L respectively. These results indicated the functional effects of honey in lowering TC and LDL with an increase in HDL, VLDL, and TG compared to the control mice group. These findings revealed the usefulness of several varieties of honey in the food and pharmaceutical companies.