The objective of this study was to investigate the usefulness of the hybrid approach using the Taguchi method (TM) and principal component analysis (PCA) in determining the optimum conditions for ultrasonic extracts of acorn leaves and green walnut husks, which potentially demonstrate the best bioactive efficiency against Bacillus cereus. First, an L-36 (2(1)x3(4)) mixed level orthogonal array design was implemented, consisting of five factors: extract type, temperature, time, solvent and concentration, respectively. Also, the total phenolic content, antiradical activity, and antibiogram analyses were investigated by design, and signal-to-noise (S/N) ratios were calculated for each trial. An analysis of variance (ANOVA) was performed using S/N ratios to estimate the effects of the measured parameters and their interactions for a single-objective TM. Following that, PCA was used to normalize the S/N ratios for each response to calculate the multi-response performance index for measuring the effects of factors on all responses. In this study, the expected optimal factor levels for each experiment were found to be different for a single-objective TM and inadequate for interpreting all responses simultaneously. The results of the study showed that the optimal conditions for all responses with PCA-based TM was found to be a 5% concentration of acorn leave extract and 50% acetone at 60 degrees C for 60min, with 136.96mg g(-1) gallic acid equivalent, 90.75% inhibited 2,2-diphenyl-1-picrylhydrazyl and 14.33mm inhibition zone against B. cereus.