Obesity, a chronic disease, resulted from excessive consumption of high-calorie foods, leading to an energy imbalance. Protium heptaphyllum (P. heptaphyllum) was used in folk medicine for its analgesic, anti-inflammatory, and healing properties. The association of the extract from P. heptaphyllum with nanotechnology was innovative for combining high technology with active ingredients that are easily accessible in the Amazon region. This study evaluated the effect of liposomes containing the ethyl acetate fraction of the crude extract of P. heptaphyllum leaves on obesity. Male Wistar rats treated with a high-calorie diet for 8 weeks to induce obesity received treatment with the liposome formulation containing P. heptaphyllum extract (1 mg/kg/day, via gavage) for 14 days. Morphological, metabolic, redox status, immunological, and histological parameters were evaluated in the adipose and liver tissue of the animals. The groups were divided as follows: C: control; P: liposomes containing extract; O: obese, and OP: obese + liposomes containing extract. The obesity model resulted in increases in body weight, caloric intake, body fat weight, and in the lipid profile. In adipose tissue, P decreased SOD (superoxide dismutase) activity in obese animals. In the liver, a positive modulation of the extract was observed in relation to glucose, amino acids, lactate, hepatoprotective action, and anti-inflammatory activity, with a decrease in interleukin 1β (IL-1β) in obese animals. The results showed an improvement in the functional and inflammatory aspects, but the treatment was not effective in alleviating general changes related to obesity, such as weight gain, fat, glucose, triglycerides, and inflammation in adipose tissue, highlighting the complexity of responses in different organs during obesity and treatment with P. heptaphyllum.