Herein, we synthesized 34 novel tryptanthrin derivatives, among which T7NHCO-series compounds showed great antibacterial activity againstXanthomonas axonopodis pv. citri,Pseudomonas syringae pv. actinidiae, andRalstonia solanacearum with EC50 values ranging from 0.26 to 0.56 mu g/mL. Meanwhile, these compounds exhibited low cytotoxicity against HEK-293. Additionally, compound T7NHCO can inhibit biofilm formation, damage bacterial morphology, downregulate the expression of bacterial chemotaxis-related proteins, cause bacterial necrosis, and effectively control citrus and kiwifruit canker (the curative and protective efficiency is 79.35 and 88.31%, respectively) diseases. However, compound T7NHCO exhibited a significant phytotoxicity to tobacco. Subsequently, based on the characteristic of tobacco wilt disease being prone to outbreak in weakly acidic soil conditions, we introduced the pH-responsive ZIF-8 drug delivery system. Fortunately, T7NHCO@ZIF-8 nanoparticles exhibited low phytotoxicity and noticeable activity against tobacco wilt disease. Above all, T7NHCO@ZIF-8 nanoparticles may be a promising green lead agent against plant bacterial diseases.