Phytosomes are used as vehicles that carry plant extracts. They exhibit biological activities and possess better bioavailability, bioabsorption, and lower toxicity than drugs. Obesity is an inflammatory state in which oxidative stress is present, which triggers severe effects on the body’s organs. This study aimed to evaluate the impact of the extract and phytosomes of Callistemon citrinus on oxidative stress and inflammation in the liver and heart of Wistar rats fed with a high-fat-fructose diet. Phytosomes containing the extract of leaves of C. citrinus were prepared. The antioxidant, pro-inflammatory enzymes, and biomarkers of oxidative stress were evaluated. Among the groups, only the high-fat-fructose group presented an increase in the COX-2, 5-LOX, and MPO inflammatory enzymes, while the XO enzyme exhibited decreased activity. The groups were fed a hypercaloric diet for 15 weeks while orlistat, C. citrinus extract, and phytosomes were administered at three different concentrations, exhibiting enzyme activities similar to those of the control group. It was also observed that the lowest concentration of phytosomes had a comparable effect to the other concentrations. Callistemon citrinus extract can modulate the activities of enzymes involved in the inflammation process. Furthermore, small doses of phytosomes can serve as anti-inflammatory agents.