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The utilization of plants with medicinal properties is deeply rooted in the traditional knowledge of diverse human populations. This study aims to investigate the cytotoxicity of nine plants commonly used by communities in San Basilio de Palenque, Bolivar (Colombia), for managing inflammation-related illnesses. Hydroethanolic extracts from various plant parts such as roots, stems, barks, or leaves were prepared through a process involving drying, powdering, and maceration in an ethanol–water (7:3) solution. The extracts were subsequently freeze-dried and dissolved in DMSO for the bioassays. Cytotoxicity against the human hepatoma HepG2 cell line was assessed using the MTT assay, with extract concentrations ranging from 0 to 500 µg/mL and treatment durations of 24 and 48 h. The total phenolic content of the nine extracts varied from 96.7 to 167.6 mg GAE/g DT. Among them, eight hydroethanolic extracts from <i>Jatropha gossypiifolia</i> L., <i>Piper peltatum</i> L., <i>Malachra alceifolia</i>, <i>Verbesina turbacensis</i>, <i>Ricinus communis</i>, <i>Desmodium incanum</i>, and <i>Dolichandra unguis-cati</i> showed low toxicity (IC₅₀ > 500 µg/mL, 24 h) against HepG2 cells. On the other hand, the extracts of <i>Aristolochia odoratissima</i> L. (IC₅₀ = 95.7 µg/mL) and <i>Picramnia latifolia</i> (IC₅₀ = 128.9 µg/mL) demonstrated the highest cytotoxicity against the HepG2 cell line, displaying a modest selectivity index when compared to the HEKn cell line after 48 h of treatment. These findings suggest that medicinal plants from San Basilio de Palenque, particularly <i>Picramnia latifolia</i> and <i>Aristolochia odoratissima</i>, have potential activity against cancer cells, highlighting their potential for further research and development.