Abstract: To explore the comprehensive effects of spraying plant growth regulators at different developmental stages on the lodging resistance, physiological and biochemical parameters, and yield of Panicum miliaceum ‘Jinshu 8’ was employed as the test material, and four plant growth regulators, prohexadione calcium, mepiquat, chlormequat chloride, and ethephon, were applied at the tillering stage and jointing stage to investigate their effects on photosynthetic characteristics, mechanical properties of stem, stem enzyme activities, stem hormone contents, and yield. The results showed that spraying prohexadione calcium at the jointing stage significantly increased the leaf area (LA) by 28.38% compared with the control. The application of the four growth regulators at both stages had no significant effect on the net photosynthetic rate (Pn), while prohexadione calcium and ethephon significantly affected the leaf's relative chlorophyll content (SPAD). The spraying of plant growth regulators significantly increased the basal stem diameter and stem-breaking strength of P. miliaceum plants. Spraying prohexadione calcium at both stages significantly reduced the lodging index of plants and significantly increased the activities of peroxidase (POD) and tyrosine ammonia-lyase (TAL) and the content of indole-3-acetic acid (IAA) in stems. Compared with the control, the application of plant growth regulators at the tillering stage and jointing stage increased the yield of P. miliaceum by 3.72%-45.08% and 28.30%-43.31%, respectively. Finally, based on the TOPSIS and RSR analyses, the efficacy of applying different plant growth regulators was evaluated, the results showed that spraying prohexadione calcium at the tillering stage and jointing stage had the best comprehensive effects on the photosynthesis, lodging resistance, and yield of P. miliaceum.