We aimed to evaluate the antidepressant activity of deoiled sunflower seeds (SFS), which are rich in tryptophan, in our mouse model and explored a possible mechanism of action. Male C57BL/6J mice were subjected to chronic unpredictable mild stress (CUMS) and were administered a diet containing SFS as the main protein source. SFS alleviated CUMS-induced depression-like behaviors, compared to the effects of a whey protein-based diet. This effect was related to increases in the levels of serotonin, dopamine, norepinephrine, acetylcholine, and brain-derived neurotrophic factor in SFS-fed mice. These changes accompanied the amelioration of inflammatory abnormalities and oxidative stress. SFS increased the aromatic amino acid levels, and the ratio of tryptophan to neutral amino acids. Furthermore, the antidepressant-like effects of SFS were involved in lipid, nucleotide, and amino acid metabolism. In summary, SFS was found to attenuate depression-like symptoms in mice. These antidepressant effects may be related to the increase in the levels of aromatic amino acids and neurotransmitters, amelioration of oxidative stress and inflammation, and the regulation of the levels of abnormal metabolites to the normal levels.