Oxidative stress plays an important role in Down syndrome (DS) pathology since the gene dose effect leads to abnormal levels of certain enzymes and metabolites. In this review, we focused on relatively easy-to-obtain, peripheral markers of oxidative stress and inflammation, in order to compare the levels of these markers in DS patients and chromosomally healthy persons. Studies taking into account age- and sex-matched control groups were of particular interest in this context. We analyzed the factors that influence the levels of said markers in both groups (i.e., the usefulness of the markers), including the age of DS patients, occurrence of regular trisomy 21 or mosaicism, physical activity of patients, and the onset of Alzheimer’s disease in DS. This paper was conceived as a handbook—to help for selecting suitable, easy-to-obtain markers for monitoring of the health status of DS patients (e.g., in nutritional studies and during dietary supplementation).