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The present study investigated the feasibility and effectiveness of pseudo-weight resistance training using mixed-reality (MR) technology for shoulder muscle activation in healthy individuals. Thirty-two healthy students aged 20~35 years participated in this preliminary study and were divided into two groups. Participants in the MR group received 30 min of training three times a week for 4 weeks using a customized MR-based pseudo-weight resistance training system. Those in the control group performed the same exercises using a conventional training program. Muscle activation of the deltoids, upper trapezius, infraspinatus, and supraspinatus were measured before and after the intervention. There was a statistically significant difference in middle deltoid, upper trapezius, and supraspinatus muscle activation in the MR group (<i>p</i> < 0.05), while the control group showed a significant difference in the anterior and middle deltoid, upper trapezius, and supraspinatus (<i>p</i> < 0.05). Regarding the between-group comparison, no statistically significant difference was observed for all six muscles (<i>p</i> > 0.05). Without any superiority of physical weight resistance training in the pseudo-weight training program, an MR-based pseudo-weight resistance training system can potentially be used for muscle-strengthening training, especially for early rehabilitation programs. However, further study using a large sample size with a long experimental duration is needed for more evidence of the presented technology and its use in home training.