•Changes of sea fennel phytochemicals during a one-year vegetation period were investigated.•Plant phenophase have impact on phenolic profile and biological activity of sea fennel extracts.•April extract with highest phenolic and chlorogenic acid level showed the best antioxidant activity.•April extract showed the best AChE inhibition and October extract the best BuChE inhibition.•PCA confirmed the relationship between the chemical compositions and biological activities. Since ancient times Crithmum maritimum L. (Apiaceae) or sea fennel, has been used in culinary practices and in folk medicine, but in the last few years it has become a rediscovered star of coastal cuisine. In this study, chemical composition (total phenolics, flavonoids, non-flavonoids, individual phenolic acids), antioxidant (FRAP, ORAC, DPPH, Briggs-Rauscher oscillating reaction) and cholinesterase (AChE, BuChE) inhibitory activities of the sea fennel samples collected in different seasons during a one-year vegetation period were investigated. The obtained results point out the great influence of the plant vegetation period on content of phenolics and consequently on plant biological activity. The sample collected before the flowering stage (in April) was, in most cases, superior in comparison to other extracts which opens a new realm of possibilities of its applications in different products and industries.