One new indole derivative, chloroindole (1), one new diketone, streptoone A (2), two new ketonic acids, streptoones B (3) and C (4), and one known macrolide antibiotic, X-14952B (5), were isolated from Streptomyces sp. SN0280. Extensive NMR, HRESIMS, and IR analysis was used to elucidate their structures. Streptoone A (2) displayed antibacterial activity (MIC value of 7.81 μg/mL) against Clavibater michiganensis, comparable with the positive control streptomycin (MIC value of 7.81 μg/mL). Streptoone B (3) showed antifungal activity (MIC value of 15.63 μg/mL) against Phytophthora capsici (positive control carbendazol MIC value of 7.81 μg/mL). These molecules provide new templates for the potential treatment and management of these phytopathogens.