The influence of ultrasonics combined with microwave thawing (UMT) and ultrasonics combined with far-infrared thawing (UIT) on the water migration and protein denaturation of red drum were studied. Five treatments were used: ultrasonics thawing (UT), microwave thawing (MT), far-infrared thawing (IT), UIT and UMT were used for thawing red drum filets. Moisture migration and protein aggregation were studied using nuclear magnetic resonance (NMR) and particle size, respectively. Raman spectra and fluorescence spectra were used to study the secondary and tertiary structure of protein. SEM was done to observe the fiber microstructure. The results showed that UMT and UIT can maintained protein stability more than other thawing methods and retained the fiber structure of the muscle. Besides, immobilized water in fiber bundles network also had no significant changes compared with fresh samples. Thus, ultrasonics combined with far infrared or microwave thawing were used to decrease protein denaturation and water migration during the thawing of Red drum fillets.