Objective: This study aimed to investigate the effects of a combined regimen of short-term mindfulness (STM) and acupressure on preoperative mood and physiological responses in patients undergoing heart valve replacement (HVR). Methods: A randomized controlled study was conducted in 62 patients admitted to the Department of Cardiac Surgery of a tertiary hospital in Guizhou from May to October 2024. Patients were randomly assigned to an intervention group or a control group, with 31 patients in each group. The intervention group received routine psychological care plus STM combined with acupressure, while the control group received routine psychological care plus a placebo intervention. Preoperative anxiety, depressive symptoms, and mindfulness level were assessed using the Amsterdam Preoperative Anxiety and Information Scale (APAIS), Self-Rating Depression Scale (SDS), and Five Facet Mindfulness Questionnaire (FFMQ), respectively. Heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were also recorded. Results: Sixty patients completed the study. After the intervention, the intervention group had lower APAIS anxiety scores and SDS scores than the control group, and higher total FFMQ scores. Scores for observing, acting with awareness, non-judging, and non-reactivity were also higher in the intervention group. In addition, SBP, DBP, and HR were lower in the intervention group than in the control group (all p < 0.05). Conclusion: STM combined with acupressure may improve mindfulness level, relieve preoperative anxiety and depressive symptoms, and help stabilize BP and HR in patients undergoing HVR. These preliminary findings suggest that this combined intervention may be a feasible adjunctive preoperative supportive strategy, but further studies with larger samples and longer follow-up are needed to verify its clinical applicability.