Infections occured in the human are mostly caused by uncontrolled growth of Staphylococcus aureus bacteria. A strategy to inhibit bacterial growth can use antibacterial agents such as chitosan. The mechanism of the effectiveness of chitosan as an antibacterial is quite complex, even the data on its antibacterial activity is quite fluctuating so that it is difficult to analyze accurately and efficiently. Therefore, the purpose of the study was to predict the inhibition zone of s.aureus bacteria through laboratory experiments combined with modeling using the Central Composite Design (CCD) approach. The research was carried out with two main stages, including chitosan isolation and calculation of bacterial inhibition zones. The production of chitosan leverages the microwave isolation and FTIR to examine for the degree of deacetylation and its functional group using. Furthermore, the antibacterial activity of chitosan biopolymer was tested using the diffusion method combined with modeling using the RSM CCD approach. The results showed that chitosam from oyster shell was obtained by DD of 83.29% and the emergence of typical chitosan groups, such as amine (NH2) and hydroxyl (OH). Chitosan can hamper the growth of s. aureus bacteria with an inhibition zone of up to 0.40 mm. The experimental data were combined with computational modeling obtained the values of the determination coefficient R2 = 0.6083. The modeling was assessed by p-value of < 0.0001 and F-value of 13.46. Statistically, the obtained model is relevant to the relationship between the number of bacterial colonies and the concentration of chitosan solution with the bacterial inhibition zone. Based on numerical analysis and modeling, the predicted values of the number of s. aureus bacterial colonies and chitosan concentrations were 550,000 CFU/ml and 42.5%. Therefore, Pearl shells can be isolated into chitosan, as well as chitosan has the potential to be a good antibacterial agent. The model has good prediction performance, but it rquires to increase the number of point spreads and it is necessary to validate the prediction results to obtain actual predictions.