• Cultivation of T.weissflogii on synthetically designed media of seawater and estradiol. • Biomass productivity and cell number declined with increase of E2 concentration in samples. • Enhanced production of protein and carbohydrate content mainly in samples T4 and T5. • The level of oxidative stress induced was assessed through MDA and other enzymatic reactions. The inefficiency of existing effluent treatment systems to eliminate pharmaceutical chemicals like endocrine disrupting estrogenic compounds from contaminated waters has raised global environmental and ecological concerns. Diatoms are unicellular, eukaryotic phytoplankton that inhabits ubiquitously and possess adaptive plasticity which enables them to withstand rapid environmental fluctuations. Thus, diatoms can be employed as indicators organisms and bioremediation agents of even trace amounts of Pharmaceutical Contaminants (PCs) like the estrogenic compounds. In this study, the influence of simulated wastewater containing pharmaceutical effluent 17-β Estradiol (E2) on the growth, cellular metabolites and oxidative stress response of the diatom, Thalassiosira weissflogii was assessed. Though an increasing concentration of the chemical displayed a negative correlation with growth, number of cells and biomass productivity; the photosynthetic profile of the diatom showed varied responses with significant enhancement in chlorophyll a and carotenoid content. The test concentrations T1 and T3 showed elevated carbohydrate and protein levels (0.82 ± 0.003 g L -1 and 2.04 ± 0.020 g L -1 ) establishing that E2 stress can be optimised to enhance primary metabolite secretion in diatoms, thereby valorizing its potential as suitable aqua feed. Besides this, an elevation in the antioxidative response against the reactive oxygen species generated was also distinctly recorded with respect to the increased release of catalase (152.70 ± 0.05–265.52 ± 0.06 k mg -1 ) and ascorbate peroxidases (0.959 ± 0.008–1.92 ± 0.021 U mg -1 ) as well as a conspicuous increment in the lipid peroxidation and hydrogen peroxide content was also there. Thus, this novel strategy of employing diatom for multitude of biorefinery aspects besides reacclimating contaminated water reveals the perspective application of this approach. .