Computational inference of affected functions, pathways and diseases for chemicals could largely accelerate the evaluation of potential effects of chemical exposure on human beings. Previously, we have developed a ChemDIS system utilizing information of interacting targets for chemical-disease inference. With the target information, testable hypotheses can be generated for experimental validation. In this work, we present an update of ChemDIS 2 system featured with more updated datasets and several new functions, including (i) custom enrichment analysis function for single omics data; (ii) multi-omics analysis function for joint analysis of multi-omics data; (iii) mixture analysis function for the identification of interaction and overall effects; (iv) web application programming interface (API) for programmed access to ChemDIS 2. The updated ChemDIS 2 system capable of analyzing more than 430 000 chemicals is expected to be useful for both drug development and risk assessment of environmental chemicals.Database URL: ChemDIS 2 is freely accessible via https://cwtung.kmu.edu.tw/chemdis.