<p><i>Acanthamoeba</i> keratitis remains a severe complication of contact lens (CL) wear, and preventing trophozoite adhesion to the lens surface is a critical step in preventing infection. This study investigated the anti-amoebic performance and ocular safety of soft CLs embedded with nephrite, a mineral with inherent antimicrobial activity. Clear, cosmetic, and nephrite-embedded CLs were compared. We uniformly dispersed nephrite powder onto the inner mold surface and encapsulated it within the polymer network using the Flusier method, preventing direct corneal exposure while maintaining transparency. In vitro assays demonstrated that nephrite-embedded CLs had significantly fewer adherent <i>Acanthamoeba lugdunensis</i> trophozoites than clear (<i>p</i> = 0.0093) and cosmetic CLs (<i>p</i> = 0.0068). SEM images showed reduced pseudopodia formation and round, contracted morphology of the attached trophozoites, suggesting early encystment. Although AFM revealed greater surface roughness than clear lenses, <i>Acanthamoeba</i> adhesion was still markedly lower. In vivo evaluation in rabbits showed no corneal opacity, no histologic inflammatory response, and no significant differences in corneal thickness or endothelial cell density compared with other groups. These findings indicate that the nephrite-embedded CLs developed in this study effectively inhibited <i>Acanthamoeba</i> adhesion while maintaining corneal safety, suggesting nephrite as a promising material for CLs with anti-amoebic properties.</p>