Purslane (Portulaca grandiflora) is a succulent plant that contains phytochemicals including flavonoids, carotenoids, polyphenolic acids, sterols, and reducing agents. The pharmacological properties of this plant include antioxidant activity, and the plant is used in sore throat and skin rashes medications, and for detoxification purposes. The plant’s secondary metabolite content is influenced by mineral nutrition. The types and amounts of plant secondary metabolites are determined by soil nutrients. Therefore, this research aimed to observe and analyze the NPK fertilizer effect on plant growth, total phenolics, and antioxidant activity in purslane. Purslane planting was carried out by applying NPK fertilizer (doses of 0, 100, 200 and 300 kg/ha) in August-October 2022 at the Green House of the Department of Biochemistry, IPB University, Indonesia. The total number of leaves and branches was found to be highest with 200 kg/ha dose of NPK fertilizer treatment. The highest total phenolic content, 0.7346 mg GAE/g FW, was found for the treatment with 100 kg/ha dose of NPK fertilizer. The highest increase in antioxidant activity was observed in extracts treated with 100 kg/ha (FRAP, CUPRAC) and 200 kg/ha (DPPH, ABTS) of NPK fertilizer. Therefore, applying NPK fertilizer at optimal doses can increase the plant growth, total phenolic content, and antioxidant activity of purslane. From the research, the recommended doses was 100 kg/ha, which gave the highest total phenolic, and the highest single electron transfer antioxidant activity (FRAP, CUPRAC). Moreover, there was no significant difference in growth parameters at higher doses.