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<i>Psophocarpus tetragonolobus</i> has long been used in traditional medicine and cuisine. In this study, <i>Psophocarpus tetragonolobus</i> extracts were isolated by maceration and ultrasound-assisted extraction and were evaluated for their antioxidant and anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The obtained results show that both extracts (maceration and ultrasound) were rich in bioactive molecules and exerted substantial antioxidant and anti-inflammatory effects. The <i>P. tetragonolobus</i> extracts’ treatment in LPS-stimulated RAW264.7 macrophages resulted in a significant downregulation of the expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β mRNA. In addition, the <i>P. tetragonolobus</i> extracts’ treatment attenuated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression. Our observations indicate that there is no significant difference between the two studied extracts of <i>P. tetragonolobus</i> in terms of biological properties (specifically, antioxidant and anti-inflammatory effects. Regardless of the extraction method, <i>P. tetragonolobus</i> could be used for treating diseases related to oxidative stress and inflammatory reactions.