The genus, native to the Americas and cultivated worldwide for culinary and medicinal purposes, includes five domesticated species with diverse fruit characteristics, pungency, and phytochemical profiles. However, the influence of casual urban backyard growing conditions on these traits remains unknown. In this study, we first assessed morphological production traits of 11 popular pepper cultivars over two growing seasons to establish a consistent baseline for cultivar performance. Next, we evaluated capsaicinoid and phenolic profiles of 47 pepper cultivars, which contribute to their pungency and antioxidant properties. Capsaicinoid profiles revealed species-specific ratios of capsaicin, dihydrocapsaicin, and nordihydrocapsaicin, with and displaying an average 64:30:6 profile, and showing a capsaicin-dominant 73:25:2 profile, and expressing a distinct dihydrocapsaicin-dominant 34:60:6 profile. Antioxidant activity positively correlated with capsaicinoid content (ABTS: R = 0.8264, < 0.0001; FRAP: R = 0.8117, < 0.0001), with (Carolina Reaper) exhibiting the highest activity (FRAP = 111.8 µM TE/g). In LPS-activated macrophages, all cultivars suppressed nitric oxide production both at the enzymatic (66-89%, < 0.001) and gene expression levels (4.2 to 5.3-fold reduction, < 0.05). Interleukin IL-1β expression was upregulated (3.8 to 12.9-fold, < 0.001), while no significant effects were noted on Cox-2, IL-6, and MCP-1 mRNA levels. These results provide novel insights into the molecular and biochemical adaptations of peppers grown in urban environments and underscore the importance of optimizing cultivation conditions to maximize their bioactive potential and health benefits.