This study investigated the vitamin C content, total phenolic compounds (TPC), and the potential bioactivities (antioxidant, antiproliferative, antibacterial activities, and inhibition capacity against N-nitrosation) of seven neglected and underutilized species (NUS): culantro (Eryngium foetidum), false roselle (Hibiscus acetosella), roselle (Hibiscus sabdariffa), tree basil (Ocimum gratissimum), Barbados Gooseberry (Pereskia aculeata), purslane (Portulaca oleracea), and tannia (Xanthosoma sagittifolium). Phenolic-rich extracts were obtained by a sequential optimization strategy (Plackett-Burman and Central Composite Design). O. gratissimum presented the highest TPC and X. sagittifolium the greater total vitamin C content. Overall, the plant extracts presented promising bioactive capacities, as scavenging capacity against HOCl, H2O2 and ROO• induced oxidation. P. oleracea demonstrated the highest cytostatic effect against ovarian and kidney tumor cells. O. gratissimum effectively inhibited S. Choleraesuis growth. Maximum inhibition on n-nitrosation was showed by O. gratissimum and E. foetidum. These results highlight the studied NUS as sources of potential health-promoting compounds.