The interactions of coffee and bread crust melanoidins with hydroxycinnamic and hydroxybenzoic acids (HCA/HBA) containing different numbers of -OH and -OCH3 groups localized at different positions on the aromatic ring were investigated. By doing so, mechanism of the interactions was intended to be explained with a structural approach. Experimental studies were carried out in DPPH radical medium. Chemometric methods were used for experimental design and multivariate data analysis. Area under the curve (AUC) values calculated from the plots of time versus inhibition (%) for coffee and bread crust melanoidins and HCA/HBA derivatives were ranged between 6532 +/- 97-19,106 +/- 85, 3997 +/- 102-7565 +/- 159 and - 1678 +/- 81-22,486 +/- 119, respectively. Synergistic interactions were revealed for both coffee and bread crust melanoidins and HCA/HBA derivatives. The significance of the concentrations of coffee and bread crust melanoidins on radical scavenging activity was clearly centered from the scores plots obtained via Principal component analysis (PCA). Phases of radical scavenging reactions were also revealed from the loadings plots.