Background and aimOverweight and obesity are associated with the development of several health complications, such as diabetes, cancer, and cardiovascular disease. Chia seed is a rich source of proteins and peptides with potential anti-inflammatory and antioxidant effects. This study aimed to evaluate the effects of digested proteins (DP) from chia seed to prevent adipogenesis and adipose tissue inflammation in mice fed a high-fat diet. Methods and resultsC57Bl/6 black mice were fed a high-fat diet plus DP (400 mg/kg of body/day) for 9 weeks. DP from chia seed reduced levels of plasma total cholesterol (−17.5%), LDL (−42.8%), triacylglycerides (−12.3%), % body fat (−26.98%), and waist circumference (−5.5%) in obese mice (p < 0.05). Furthermore, treatment with DP reduced (p < 0.05) adipocytes area, foci of inflammation, levels of p-NF-κB p65, PPARγ, mRNA SREBP1 (sterol regulatory element-binding transcription), and TNF-α. DP also increased mRNA adiponectin on adipose tissue in animals DP-treated, compared with no-DP-treated animals. However, mRNA LPL and HDL levels were not changed (p > 0.05). The peptides from DP had in silico high interaction with metalloproteinase-2. ConclusionsWhen using this experimental model, DP from chia seed had an anti-inflammatory and anti-adipogenic effect. These results suggest the effectiveness of digested proteins from chia seed against central obesity and its associated inflammation.