The antioxidant activities (in vitro) of vacuum-packaged dry-cured sausages stored for 1 year, which were treated with varying concentrations of extracts from orange peel (EFOP) in a modification solution, were evaluated using a central composite design. The individual variables: soy lecithin concentration, soy oil concentration, treated time, lactic acid addition, EFOP addition, and dependent variable [i.e., in vitro antioxidant activity] were analyzed by response surface methodology. Among the 32 treatment combinations, treatment 26 (central point) exhibited a higher 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity compared to the control group (natural hog casing without modification). Spectral pre-treatments were applied to enhance the robustness of the model, and a partial least squares regression model (PLSRM) was fitted. The results of the response surface methodology indicated that the interactive effects of a high [soy lecithin concentration] × a high [EFOP addition] yielded a DPPH assay result of over 35%. The determination coefficients (R2 value) of the second-order polynomial model for the simultaneous effects on in vitro antioxidant activity reached 65.28%. The PLSRM developed using average reflectance data after the first derivation pre-treatment demonstrated a higher R2 value in the calibration group compared to the untreated data. The first principal component accounted for 77.39% of the overall attributes and effectively differentiated the sausages’ antioxidant activity from 31.88%.