The increasing use of plant defense stimulators (PDS) and biostimulants (BS) to make agriculture more sustainable has led to questions about their action on plants. A new PhysBioGen approach is proposed with complementary tools: PHYSiological (root weight); BIOchemical and BIOlogical (secondary metabolite quantification and Plasmopara viticola development) and expressions of 161 GENes involved in metabolic plant functions. The proposed approach investigated the effects of three phytostimulants on Vitis vinifera: one PDS (ASM) and one BS chelated (CH) and another enriched with seaweed (SW). Distinct responses were obtained between the PDS and the two BS. In particular, we observed the persistence of anti-mildew efficacy over time, correlated with differentiated expressions of defense genes (VvROMT, VvSAMT, VvPR8). As expected, the two BS displayed more similarities to each other than to the PDS (flavonols, anthocyanins, free salicylic acid). However, the two BS revealed differences in the modulation of genes involved in defense and primary metabolism and some genes were identified as potential markers of their action (VvWRKY1, VvLOX9, VvPOD, VvPDV1, VvXIP1, VVDnaJ). Our results highlight the common and the specific effects of the two BS and the PDS. These new tools could help in understanding the mode of action of phytostimulants in order to achieve better quality and production yield and/or as a way to limit chemical inputs in the vineyard.