Foxtail millet ( Setaria italic L.) is an important food and fodder crop that is cultivated worldwide. Quantifying the effects of herbicides on foxtail millet is critical for safe herbicide application. In this study, we analyzed the effects of different fluroxypyr dosages on the growth parameters and physiological parametric of foxtail millet, that is, peroxidation characteristics, photosynthetic characteristics, and endogenous hormone production, by using multivariate statistical analysis. Indicators were screened via Fisher discriminant analysis, and the growth parameters, peroxidation characteristics, photosynthesis characteristics and endogenous hormones of foxtail millet at different fluroxypyr dosages were comprehensively evaluated by principal component analysis. On the basis of the results of principal component analysis, the cumulative contribution rate of the first two principal component factors was 93.72%. The first principal component, which explained 59.23% of total variance, was selected to represent the photosynthetic characteristics and endogenous hormones of foxtail millet. The second principal component, which explained 34.49% of total variance, represented the growth parameters of foxtail millet. According to the principal component analysis, the indexes were simplified into comprehensive index Z , and the mathematical model of comprehensive index Z was set as F = 0.592 Z 1 + 0.345 Z 2 . The results showed that the comprehensive evaluation score of fluroxypyr at moderate concentrations was higher than at high concentrations. Consequently, one L (active ingredient, ai) ha −1 fluroxypyr exerted minimal effects on growth parameters, oxidase activity, photosynthetic activity, and endogenous hormones, and had highest value of comprehensive evaluation, which had efficient and safe benefits in foxtail millet field.