The development of a method for the soft and ecological synthesis of ZnO is a key research area in materials science and engineering. Herein, a simple and ecofriendly gelation method via biopolymer (sodium alginate) was investigated to highly control the size, morphology, and porosity of synthesized ZnO nanoparticles (ZnO NPs). The characterization techniques used confirmed the formation of pure ZnO with a wurtzite structure and an average particle size of 44.8 nm. Furthermore, the effect of different parameters (solution pH, ZnO quantity and dye concentration) on the photocatalytic performances of ZnO NPs was evaluated using the design of experiments. A three-factor Doehlert design experiment was conducted to investigate the optimal conditions for Orange G photodegradation using ZnO NPs. The Doehlert design was used as a statistical method to systematically vary the values of these three factors and evaluate their effects on photodegradation. The experimental results showed that the optimal photodegradation conditions obtained at a ZnO quantity of 1.03 g/L, an orange G concentration of 39.4 µM, and an initial pH of 4.2.