The inclusion complexes of the salsalate drug (SLT) with β-cyclodextrin derivatives (β-CDs); namely, β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HPβ-CD), and sulfobutylether-β-cyclodextrin (SBEβ-CD) are synthesized using the ultrasound process. The enhanced aqueous solubility of SLT is demonstrated by phase solubility diagram and optical spectroscopy, showing the inclusion complexation of β-CDs and SLT with a 1:1 stoichiometry. The β-CDs:SLT inclusion complexes exhibit potent bacterial activity against Staphylococcus aureus and Escherichia coli and reduce the cytotoxic effects of SLT on MCF-7 cells. The β-CDs:SLT complexes display further important activity for the inhibition of α-amylase and α-glucosidase, indicating their antidiabetic capability. The designed and synthesized inclusion complexes of SLT with β-CDs are widely expected to have potential applications in the preparation of novel pharmaceutical formulations containing SLT. © 2018 Elsevier B.V.