This study investigated ameliorative effects of dietary oyster mushroom (Pleurotus ostreatus) spent substrate (OMSS) in broiler chickens fed diets supplemented with combined marula seed cake (MSC) and mucuna seed meal (MSM) replacing soya bean meal (SBM). In a completely randomised design (CRD), 400 day-old Ross 308 chicks were randomly allocated to 5 iso-nitrogenous-energetic diets (control with 100% SBM, control with 60% MSC and 40% MSM replacing SBM (MSC + MSM), MSC + MSM with 1.25% OMSS, MSC + MSM with 2.5% OMSS, and MSC + MSM with 5% OMSS) each with 8 replicate pens of 10 during starter, grower and finisher phases. Dietary MSC + MSM decreased (P < 0.001) feed intake (FI), body weight gain (BWG), and feed conversion efficiency (FCE); slaughter weight, hot carcass weight (HCW), cold carcass weight (CCW), breast weight, and back lengths (P < 0.001); serum SDMA and alanine transaminase (P < 0.05). In contrast, it increased the weights of the thigh (P < 0.001), wing (P < 0.01), liver (P < 0.001), proventriculus (P < 0.001), gizzard (P < 0.001), duodenum (P < 0.001), jejunum (P < 0.001), ileum (P < 0.001), and caecum (P < 0.01) and serum alkaline phosphatase (P < 0.05) and cholesterol (P < 0.01). Further, it increased meat redness and decreased its hue angle at 45 min post-slaughter (P < 0.01) whilst it decreased its pH (P < 0.01) and increased its shear force (P < 0.05) at 24 h post-slaughter. Compared to higher levels, low (1.25%) dietary OMSS improved, though limitedly, FI, BWG, and FCE at grower and finisher phases only (P < 0.001) whilst it reversed MSC plus MSM-induced deleterious effects on slaughter weight, HCW, and CCW (P < 0.001) and increases in gizzard weight (P < 0.001) and meat shear force at 24 h post-slaughter (P < 0.05). Otherwise, OMSS generally decreased (P < 0.05) serum SDMA and alanine transaminase whilst it abrogated and augmented increases in serum alkaline phosphatase (P < 0.05) and cholesterol (P < 0.01), respectively, and reversed the increase and decrease in meat redness (P < 0.01) and hue angle (P < 0.05), respectively. In conclusion, dietary replacement of SBM with combined MSC plus MSM induced deleterious effects in broiler chickens that were limitedly abrogated by low (1.25%) inclusion level of OMSS.