Development of obesity is associated with excessive fat accumulation and oxidative stress along with chronic inflammation. Goji berries (Lycium barbarum) are high in polyphenolic compounds and have anti-inflammatory, anti-oxidant, and hypolipidemic properties that may alleviate the pathogenesis of obesity and related metabolic complications. Thus, the aim of this study was to investigate potential metabolic benefits of GB supplementation against high fat (HF) diet-induced obesity and its comorbidities in HF diet-fed rats (male Sprague–Dawley, n = 8/group, 6 weeks old). We also sought to examine the potential metabolic benefits of fermented GB (FGB) with L. plantarum CB3 and possible distinctions in the degree and/or mechanism of action compared to GB. GB and FGB supplementation suppressed the gene expression of inflammation indices at the local (adipose tissues) and systemic (liver) levels. In addition, GB and FGB supplementation upregulated the gene expression of antioxidant enzymes compared to the HF and/or even low fat (LF) group with more remarkable antioxidant effects by GB supplementation. Also, GB and FGB supplementation protected from HF-induced damages of the liver and dyslipidemia. In conclusion, we demonstrated that GB and FGB supplementation protected from HF-induced metabolic complications primarily by improving hepatic function and corresponding lipid metabolism via their anti-inflammatory and antioxidant properties. To our knowledge, this is the first in vivo study confirming metabolic benefits of GB in a fermented form. Thus, these findings support the potential application of both GB and FGB to ameliorate obesity-associated metabolic abnormalities.