Soil worms are among the most abundant and functionally diverse soil animals. However, they have been largely overlooked in studies on microplastic (MP) toxicity. MPs and plant secondary metabolites (PSMs) are ubiquitous in soil due to plant litter decomposition and heavy MP contamination, inevitably interacting and exerting combined toxicity on soil organisms. However, little research has been conducted on their joint effects. This study investigates the individual and combined toxic effects of polyethylene (PE) MPs and three PSMs (glycyrrhizic acid, tannic acid, and matrine) on the model organism Caenorhabditis elegans. Physiological and biochemical responses were assessed using fluorescence microscopy, image analysis, and statistical methods. After 42 hours of exposure to PE MPs and/or PSMs, worm growth and development were negatively impacted. Under experimental conditions, matrine and PE MPs synergistically inhibited worm growth, exacerbated neurological damage, and induced oxidative stress. In contrast, glycyrrhizic acid and tannic acid alleviated PE MP-induced growth inhibition, mitigated oxidative stress, and demonstrated antioxidant properties that counteracted oxidative damage. This study offers new insights into the combined effects of MPs and PSMs in soil ecosystems, contributing to ecological risk assessments and pollution management strategies.