Natural biostimulants, such as seaweed extracts, can stimulate plant growth and development in both model and crop plants. Due to the increasing demands for their use in agriculture, it is crucial to ensure the sustainability of the sources from which they are produced. Furthermore, some seaweed extracts were recently shown to prime and protect from adverse environmental factors such as drought, salinity and extreme temperatures, as well as from oxidative stress. The molecular mode of action of these biostimulants has still not been fully elucidated, but there has been significant progress in this direction in the last years. Firstly, this review examines the sustainability aspects of harvesting seaweed resources as raw materials for manufacturing biostimulants and provides an overview of the regulatory landscape pertaining to seaweed-based biostimulants. The review then summarises the recent advances in determining the genetic and molecular mechanisms activated by seaweed-based biostimulants, their influence on transcriptome reconfiguration, metabolite adjustment, and ultimately stress protection, improved nutrient uptake, and plant growth and performance. This knowledge is important for deciphering the intricate stress signalling network modulated by seaweed-based biostimulants and can aid in designing molecular priming technologies for crop improvement.