Persimmon leaves usually as agricultural and forestry waste were fermented by Lactiplantibacillus plantarum and Saccharomyces cerevisiae. Growth and metabolic performances of L. plantarum and S. cerevisiae, as well as the effect of fermentation on the antioxidant abilities of the extract was investigated, including the content of flavonoids, 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical clearance rates. Growth of L. plantarum was limited, even though the acid production was sustainable, while S. cerevisiae was more suitable to inhabit in the persimmon leaves extract. A symbiotic relationship was observed between the two microbes, reflected in aspects of growth of S. cerevisiae, pH reduction, and ethanol production. The DPPH radical clearance rates of all groups decreased at the early period, and increased later. The co-culture group reached the second highest value of DPPH radical clearance rate only next to the single group of L. plantarum at 9 h. All groups showed an overall downward trend of the hydroxyl radical clearance rates during the 9 h-fermentation. These findings highlight the promising industrial application of fermentation of the plant-based materials with Lactiplantibacillus and Saccharomyces species to improve the biological properties.