<p>Patients with multiple myeloma (MM) often experience psychological distress and reduced quality of life (QoL), but evidence for teach-back–based education in MM is limited. We tested a teach-back–centered multidimensional intervention in hospitalized patients. This single-center prospective controlled study enrolled 195 inpatients. The intervention group (n = 101) received teach-back–guided disease education plus psychological and lifestyle support, in addition to usual care. Controls (n = 94) received usual care alone. Outcomes included QoL (EORTC QLQ-C30), anxiety, depression, anger, disease knowledge, C-reactive protein (CRP), and immunoglobulin G (IgG). Linear mixed-effects models estimated group differences; Hedges g was reported. QoL improved in both groups, with an additional benefit in the intervention group (Time×Group β = 0.705; 95% CI 0.261–1.149; P = 0.004; Hedges g = 0.251). Anxiety, depression, and anger decreased in both groups; the intervention group showed larger reductions in anxiety (β = −0.173; 95% CI − 0.341 to − 0.006; P = 0.009; g = − 0.117), depression (β = −0.177; 95% CI − 0.352 to − 0.003; P = 0.046; g = − 0.112), and anger (β = −0.567; 95% CI − 0.732 to − 0.002; P = 0.038; g = − 0.682). Disease knowledge increased without a between-group difference (β = 0.183; P = 0.657). Exploratory analyses suggested larger reductions in CRP (β = −3.442; 95% CI − 6.296 to − 1.411; P = 0.014) and IgG (β = −0.632; 95% CI − 0.988 to − 0.276; P = 0.043). A teach-back centred multidimensional intervention improved QoL and emotional outcomes beyond usual care. The observed between-group differences in CRP and IgG were exploratory associations. Future multicentre randomised studies with longer follow-up are needed to confirm the durability and generalisability of the QoL and emotional benefits observed in this study.</p> Graphical Abstract <p></p>