Scientists consider saltwater one of the effective environmental stress that negatively affects the growth and establishment of trees and shrubs worldwide. Utilizing the potential of Bio-stimulant compounds present in the brown seaweed extract is an alternative strategy to improve crop tolerance to salinity. This study focused on the application of seaweed extract as a Bio-stimulant agent to counteract the salt stress on the growth and some physiochemical aspects of milkweed seedlings. In this experiment, the seedlings were treated with seaweed extract (SWE) of Sargassum angustifolium at four concentrations (non-SWE or control, 0.5, 1.0, and 1.5%) and then exposed to salt stress at four levels (0, 7.5, 15, and 30 dS m−1 of diluted seawater) in a completely randomized design (four replications per treatment) over a time-span of 3 months. The results indicated that SWE-treated seedlings could tolerate salinity up to 15 dS m−1 and also increase the survival rate by 69%. The growth parameters like height, specific leaf area, root length and volume, root and shoot dry weight were considerably enhanced by SWE (1%) from 7.5 to 30 dS m−1. Moreover, gas exchanges and chlorophyll pigments were markedly increased using SWE (0.5%) under salt lower 15 dS m−1 than control. Also, both SWE and salt stress significantly enhanced antioxidant enzymes over control, but SWE more increased the parameters. SWEs agent at different dosages significantly decreased electrolyte leakage at all salinity levels (except in 7.5 and 15 dS m−1) compared to control. SWEs (1%) resulted in increasing K+ uptake but decreasing Na+ uptake and markedly enhancing K+/Na+ ratio in stressed-milkweed versus free-salt stress. Totally, this research illustrates the potential of SWEs (at lower dosages) for elevating milkweed tolerance to moderate salinity stress and highlights the possibility of applying it as Bio-stimulant fertilizer.