Down syndrome (DS) is considered as the most prevalent cause of mental retardation. Possible causes of DS are nondisjunction of human chromosome 21 (Hsa21) or a Robertsonian translocation between Hsa21 and another chromosome. Scientists are trying to develop drugs to rescue learning performance in DS disease. In the last few years, a large number of drugs and small molecules have been shown to recover one or more abnormalities in transgenic mouse models. In this study, the effect of memantine and RO4938581 drugs on rescued learning was determined by evaluating the protein expression level of the transgenic mouse model using machine learning algorithm techniques. Gene set enrichment analysis (GSEA) was performed and both drugs were found to have an effect on common gene ontology (GO) terms. Thanks to the applied methodology and the result of this study, it may be possible to diagnose and treat the disease by developing a new drug that stimulates areas where the common GO terms are precisely determined.