Many people worldwide use plants, alone or in combination with their antihyperglycemic drugs, to manage their type 2 diabetes mellitus [1][2]. Most researches on therapeutic properties of herbs are carrying out on methanolic or ethanolic extracts [3]. However, these studies are not representative of the population consumption habits. For the first time, a study was performed with specimens of the two mostly used species in Guadeloupe: Phyllanthus amarus and Phyllanthus debilis. The chemical composition of aqueous infusion of dried aerial parts were evaluated in relationship to antidiabetic mechanisms occurring at the level of glucose homeostasis in cultured hepatocytes (H4IIE) and muscle cells (C2C12). On the one hand, the extracts of P. amarus showed a significant activity in glucose uptake on muscle cells with an increase of 23.11 ± 3.84 % whereas it was no significant for P. debilis (13.4 ± 3.28 %). On the other hand, the same extracts of P. debilis showed stronger inhibition of hepatocellular G6Pase activity (65.88 ± 4.28 %), close to the action of insulin (64.29 ± 4.59 %), than P. amarus extracts (34.6 ± 1.45 %). The comparison of their chemical composition demonstrated the presence of polyphenols, especially hydrolyzable ellagitannins, involved in their antidiabetic effects. Only four molecules were common to both species, galactaric acid lactone, gallic acid, 5-O-(E)-caffeoyl galactaric acid, a new compound found for the first time in both species, and geraniin. The study of the antidiabetic activity of geraniin, which is predominant in P. debilis, showed a significant inhibition of G6Pase (60.67 ± 2.33 %) whereas no significant activity was observed for glucose uptake. These results suggest that this compound greatly influence the antidiabetic effects of the Phyllanthus crude extracts. [1] Genthon, L. (2014). Contribution à l’étude de la connaissance et de l’utilisation des plantes de la pharmacopée locale par la population guadeloupéenne. [2] Patel, J. R., Tripathi, P., Sharma, V., Chauhan, N. S., & Dixit, V. K. (2011b). Phyllanthus amarus: Ethnomedicinal uses, phytochemistry and pharmacology: A review. Journal of Ethnopharmacology, 138(2), 286-313. doi:http://dx.doi.org/10.1016/j.jep.2011.09.040 [3] Kumaran, A., & Joel Karunakaran, R. (2007). In vitro antioxidant activities of methanol extracts of five Phyllanthus species from India. LWT - Food Science and Technology, 40(2), 344-352. doi:http://dx.doi.org/10.1016/j.lwt.2005.09.011