This study sets out to investigate the impact of monetary policy on deposit money banks’  profitability in Nigeria. The objectives are to examine the relationship between Cash Reserve ratio (CRR), liquidity ratio (LQR), Monetary Policy Rate (MPR) and money supply (MSP) and return on assets of deposit money banks in Nigeria. Data were collected through Central bank of Nigeria Statistical Bulletin from 1985 to 2021.  Analysis were carried out using OLS, Cointegration and Error correction model (ECM) were adopted for further analysis. Findings revealed that: there is positive but no significant relationship between Cash Reserve ratio (CRR) and return on assets of deposit money banks in Nigeria; liquidity ratio (LQR) has positive but no significant impact on return on assets of deposit money banks in Nigeria; there is positive but no significant relationship between Monetary Policy Rate (MPR) and return on assets of deposit money banks in Nigeria; and there is negative and no significant relationship between money supply (MSP) and return on asset of deposit money banks in Nigeria. Based on the findings, the study recommends that the CBN should continuously adopt all instruments investigated in this study to regulate banking activities.