A collection of by-products was surveyed for novel biostimulant and biopesticide activity by establishing a screening platform (Bio2Bio) that integrated a broad spectrum of in vitro and in planta bioassays. Here, we report plant growth-promoting and biopesticide activities obtained from four solvent extracts of maize distillers’ dried grains with solubles (DDGS), a bioethanol fermentation by-product. The hexane extract stimulated Arabidopsis primary root growth, whereas the ethanol extract enhanced tomato shoot growth and fresh biomass. The water extract showed fungicide, acaricide, nematicide, and protective activities, specifically conferring disease tolerance by inducing the plant immune response. We demonstrate significant biopesticide effects of DDGS water extract against the fungus Magnaporthe oryzae (32 % in vitro efficacy), oomycete Phytophthora infestans (73 % in planta efficacy), and spider mite Tetranychus urticae (60 % in vitro efficacy), as well as plant-induced resistance against the fungal pathogen Botrytis cinerea (30 % in planta efficacy) and root-knot nematode Meloidogyne graminicola (91 % in vitro and 50 % in planta efficacy). The broad range of bioactivities suggests that DDGS is a complex mixture composed of a wide variety of plant metabolites. DDGS represents a valuable source for discovering bioactive ingredients with potential use as biostimulants and/or biopesticides.