Portulaca oleracea L. is a wild edible plant with high potential for exploitation in commercial cropping systems due to its nutritional value and great adaptability to abiotic stress conditions. The present study aimed to investigate the response of purslane plants grown under drought stress conditions (100%, 80%, and 60% of field capacity (FC)) and the implementation of biostimulant amendments (control without amendment, plant growth-promoting rhizobacteria (PGPR), mycorrhiza, and effective microorganisms (EMs)) for two consecutive years. In the two-year experiment, the greatest height was recorded in plants grown under no-stress conditions and inoculated with PGPR. The highest branch number, and fresh and dry weight of aboveground and underground parts were observed under no-stress conditions at the mycorrhiza treatment. Moreover, mycorrhiza application in plants growing under 100% FC resulted in the highest N, P, total carbohydrates, and vitamin C and the lowest nitrate and proline contents in leaves. Purslane plants grown under 100% FC and inoculated with PGPR treatment resulted in the highest K and total chlorophyll leaf contents. Additionally, growing plants under mild drought stress (80% FC) combined with biostimulant application (e.g., inoculation with mycorrhiza, PGPR, and EM) may improve plant growth characteristics and mitigate negative stress effects. In general, the applied biostimulant amendments alleviated the adverse effects of drought on plant growth and leaf chemical composition indicating the importance of sustainable strategies to achieve high yield and sufficient quality within the climate change scenario.