Objective: This study aims to synthesize a series of five new Mannich bases of dehydrozingerone (DHZ) derivatives and to evaluate for their antiinflammatory and antioxidant activity. Methods:The synthesis was performed by refluxing DHZ with formaldehyde and secondary amines, and the structures of the synthesized compounds were confirmed by FT-IR,1H-NMR,13C-NMR, and HR-MS.The anti-inflammatory and antioxidant activity evaluations were done by inhibition of heat-induced albumin denaturation and a free-radical DPPH method, respectively. Results: All the synthesized compounds (2a-e) showed anti-inflammatory and antioxidant activity. The highest anti-inflammatory activity was shown by compound 2c.The activity was comparable to the that of diclofenac sodium as a standard. While, the highest antioxidant activity was demostrated by compound 2e. The compound showed moderate activity compared to that of quercetin as a standard. Mostly of Mannich base derivatives of DHZ compounds exhibited higher antioxidant activity than that of DHZ. Conclusion: A series of five new Mannich bases of DHZ (2a-e) was synthesized successfully. Compound 2c demonstrated anti-inflammatory activity which was comparable to diclofenac sodium, while compound 2e exhibited moderate antioxidant activity compared to quercetin as standard. © 2018 EManuscript Technologies. All rights reserved.