BACKGROUND: The presence of insoluble calcium oxalate druse crystals (CaOx) in sweet potato (Ipomoea batatas) can negatively affect its nutritional quality. Photosynthesis, starch, and protein composition are linked with oxalate synthesis and tuber quality under water scarcity. Our main objective was the oxalate quantitation of sweet potato tubers and shoots and also to assess how drought changes their nutritional value. Eight sweet potato accessions from Madeira, the Canaries and Guinea-Bissau were analyzed for their response to drought stress. Tubers and shoots were analyzed for total (T-Ox), soluble (S-Ox) and insoluble (CaOx) oxalates, protein, chlorophyll content index (CCI), soluble starch, starch swelling power, and starch solubility in water. RESULTS: The S-Ox and CaOx content was higher in shoots. Six accessions were above maximum CaOx levels for raw consumption. Accessions with more favorable responses to drought had decreased CaOx with S-Ox increase content for osmoregulation. They also presented slightly decreased CCI and protein contents. These accessions also had an increased shoot starch content, for further tuber storage starch hydrolysis, and maintained the quality and functional properties of the tuber starch grain. Those with a less favorable response to drought had a higher T-Ox and CaOx content in both organs, hindering water absorption. They also had decreased protein and CCI, with a slight increase in tuber starch hydrolysis. CONCLUSION: Oxalate content was significantly related to carbohydrate metabolism, CCI, and protein synthesis. This study significantly contributed to the screening of the sweet potato stress response to drought, to adapt this crop to climatic change through breeding programs.