Seaweeds are the diverse groups of macroalgae that inhabit the marine habitat and play a prominent role in the intertidal region ecosystem. Seaweeds are exposed to various environmental stresses and acclimatize through the regulation of genomic, proteomic, and metabolomic components. Under various stresses, they show changes in protein composition due to upregulation and downregulation of genomic components. Proteins are directly involved in stress response; therefore, proteomics studies provide a detailed insight into de novo protein synthesis, protein abundance, and stress acclimatization. Gene expression studies played a dignitary role in the previous times until it was observed that the expressed genes are not always involved in protein production; hence, proteins are the vital components at the cellular level. A copious amount of work has been carried out on protein profiling in higher plants; however, studies on seaweeds to understand the complex protein network that plays an important role during stress acclimatization are scarce. Phosphomannomutase (PMM) has been identified to be upregulated under the hyposaline condition in Sargassum fusiforme. PMM has been reported to be involved in cell wall polysaccharide synthesis, thus helping in acclimatization through cell wall buffering capacity. Aldehyde dehydrogenase has also been identified from Pyropia yezoensis, which neutralizes the accumulated aldehydes under oxidative stress. Proteomics provides strong clues for responses at different levels in seaweeds under different environmental stresses. This chapter focuses on proteomics studies in seaweed under environmental stresses and also provides a comprehensive insight into the recent developments in proteomics and their use in seaweed cultivation.