Despite microbe-based products for grapevine protection and growth improvement are already available, a few of them contain microbes directly isolated from vine tissues. For this reason, a collection of endophytic bacterial isolates obtained directly from grapevine woody tissues has been used for producing anad-hocinoculum. The selected bacterial isolates were tested in biocontrol assays against some of the main grapevine pathogens (e.g.,Botrytis cinerea,Guignardia bidwellii,Neofusicoccum parvum) and the best performing ones were screened for plant growth promoting (PGP)-traits (e.g., phosphorous solubilization, indole-acetic acid and siderophore production). Before being planted, rooted cuttings were inoculated with two different synthetic communities: the first one was anad-hocdeveloped microbial community (SynCom), whereas the second was a commercial consortium formed by arbuscular mycorrhizal fungi (AMF) and a rhizosphere bacterial strain (AMF+B). Physiological parameters were monitored to evaluate effects on plant performances, and samples for biochemical and molecular analyses were collected. Integration of physiological data with metabolite profiling and transcriptome sequencing highlighted that the SynCom treatment shaped the plant growth-defence trade-off, by regulating photosynthesis and diverting energy sources towards the activation of defence metabolic pathways. On the other hand, the AMF+B treatment led to a more balanced growth-defence trade-off, though a mild activation of defence mechanisms was also observed in these plants. Our findings suggest that an experimental approach considering both the features of associated microbes and their impacts on plant growth and defence could shed light on the “dark-side effects” of SynCom application, thereby enabling their exploitation with a refined awareness.