The stigmas of the medicinal plant Crocus sativus are utilized as an expensive traditional Chinese medicine to treat irregular menstruation, depression, postpartum thrombosis, and bruises. As one of the most severe diseases of C. sativus, corm rot has hindered development of the C. sativus industry. Synthetic microbial communities (SMCs) have shown significant promise for the control of plant diseases, but there are few reports on their use for control of C. sativus corm rot. In this study, we co-cultured pairs of C. sativus rhizosphere soil-isolated fungi and bacteria, performed compatibility experiments on them to obtain SMCs with good compatibility, and evaluated their ability to improve disease resistance against C. sativus corm rot induced by Fusarium oxysporum. The fermentation broth of the most effective SMC was partitioned into five fractions, and disease resistance activity assays were conducted to identify the fraction in which active metabolites were concentrated. Metabolomic analyses were carried out to analyze the chemical composition of this fraction and determine how it differed from that of single cultures. We constructed four SMCs and found that SMC03 (Trichoderma yunnanense SR38 + Paenibacillus peoriae SR235) showed the best disease resistance activity, which was significantly higher than that of SR38 or SR235 alone (P < 0.05). The active metabolites produced by SMC03 were mainly concentrated in the aqueous fraction, which contained abundant organic acids and their derivatives. Co-cultivation of SR38 and SR235 increased overall production of DL-3-phenyllactic acid, 3-hydroxydecanoic acid, and (2S)-2-isopropylmalate, and we speculate that these components can bind membrane receptors of plant cells, induce local resistance, and subsequently generate plant immune response, thereby enhancing C. sativus disease resistance. In summary, co-cultivation of a fungus and a bacterium from the C. sativus rhizosphere may enhance host resistance to corm rot by accelerating the synthesis of certain organic acids. This study demonstrates for the first time the feasibility of developing SMCs for control of corm rot in C. sativus, which is of great significance in guiding the development of efficient biocontrol agents against C. sativus corm rot, thereby promoting sustainable cultivation of C. sativus. These findings also provide reference for the biocontrol of fungal diseases in other field cultivated medicinal plants.