As the most frequently used archival materials for painting and recording, paper lays the groundwork for the development of prosperous human civilization. However, its susceptibility to three primary factors including external ultraviolet light, increased acidity, and biological pathogens in long-term storage shortens the longevity of paper. Therefore, the protection of paper-based cultural relics is extremely urgent. Inspired by the three adverse factors affecting the protection of cultural relics, we herein propose to combine the ultraviolet absorber 2-hydroxy-4-(octyloxy)benzophenone (UV-531) and alkaline zinc oxide (ZnO) nanoparticles innovatively into the antibacterial agent polyhexamethylene biguanidine hydrochloride (PHMB) to realize the strategy of three birds with one stone for relics protection. This study illustrates that the tensile strength and the folding endurance of different test papers are guaranteed by coating them with the composite reagents, and molds including Mucor, Trichoderma, and Aspergillus niger are effectually sterilized. In addition, a hand-painted Chinese ink-wash painting with beautiful flowers is chosen as the object for simulating cultural relics protection, and negligible color fading is observed in aging experiments. From the perspective of effectiveness, simplicity, and economy, this strategy sheds light on preservative protection of paper-based relics in long-term storage.