Seed germination is a crucial stage in the life cycle of annuals in arid, saline regions and is particularly vulnerable to abiotic stresses. Peganum harmala, a valuable medicinal plant, has limited research on its seed germination response to different environmental stresses in the arid, saline regions of Central Asia. To investigate this, we studied the effects of various temperature regimes (ranging from 20/5 to 35/20 °C), light exposure (12 hours light/12 hours dark and continuous dark), seven levels of polyethylene glycol (PEG-6000) concentration (ranging from 0–30%), and four types of salinity (ranging from 0–600 mmol L−1). Our findings show that photoperiod and temperature significantly influence germination. Optimal temperature range for seed germination was observed at 30/15 °C, with simulated critical and limit values of drought tolerance being highest (17.30% and 24.98%). However, higher temperatures (35/20 °C) and lower temperatures (20/5 °C) reduced the critical and limit values of drought tolerance. Additionally, the type and concentration of salinity had a significant effect on the seed germination, shoot, and root lengths of P. harmala. Regression analysis indicated that the critical values of NaCl, Na2SO4, NaHCO3, and Na2CO3 tolerance during germination were 178 mmol L−1, 101 mmol L−1, 106 mmol L−1, and 54 mmol L−1, respectively. Salinity inhibition on seed germination followed the order: NaCl < NaHCO3 < Na2SO4 < Na2CO3. Moreover, NaCl, Na2SO4, NaHCO3, and Na2CO3 significantly inhibited the growth of P. harmala seedlings in both shoots and roots. Our study demonstrates the sensitivity of P. harmala to environmental factors such as light, temperature, drought, and salinity. The study provides valuable information on the germination ecology of P. harmala under diverse ecological scenarios, which can be useful in developing efficient propagation and utilization of this medicinal plant.