The aim of this study was to determine and compare the effectiveness of transdiagnostic therapy with progressive muscle relaxation (PMR) techniques on emotion regulation strategies, self-compassion, maternal role adaptation, and social and work adjustment in mothers of premature infants. The current study is a randomized controlled clinical trial with two groups and pre-test, post-test, and a two-month follow-up assessment. This study included 27 mothers who were randomly assigned to either the transdiagnostic therapy group or the PMR techniquesgroup (13 people in the transdiagnostic group and 14 people in the PMR techniques group). The experimental group received eight sessions of transdiagnostic therapy while the control group received eight sessions of PMR techniques. The participants completed the following measurement tools: Emotion Regulation Questionnaire, Self-Compassion Scale, Maternal Role Adaptation Scale, and Work and Social Adjustment Scale. Transdiagnostic therapy was significantly more effective than PMR techniquesin improving emotion regulation strategies, self-compassion, maternal role adaptation, and social and work adjustment in the between-group comparison conducted at post-test and follow-up (p < 0.01). In these preliminary analyses, transdiagnostic therapy was shown to be effective in improving the emotional health of mothers with premature infants and more effective than PMRtechniques.