The Indo-Pacific warm pool is the warmest and most dynamic ocean–atmosphere-climate system on Earth and was subject to significant climate changes during the Pleistocene glacial-interglacial transitions. This has been shown to significantly affected the strength of surface waters that redistribute heat from the tropics to the southern part of the Indian Ocean. Here we investigate the response of the oceanic circulation at intermediate depth (1200 m) of the eastern equatorial Indian Ocean (EEIO) with neodymium (Nd) isotopes in the context of the climatic oscillation of the last 500 ka. The most striking feature of our new dataset is the seesaw Nd record that mimics glacial-interglacial cycles. While the interglacial periods are characterized by a higher contribution of the less radiogenic neodymium (~ − 7ε _Nd ) Antarctic Intermediate Water (AAIW), the glacial periods are characterized by more radiogenic water mass of Pacific origin (~ − 5ε _Nd ). To explain the increase in the ε _Nd signature toward a more radiogenic signature as the Indo-Pacific connection is reduced under the low sea level of the glacial periods, we show that under global cooling, the AAIW advances northward into the tropics, which is a consequence of the general slowdown of the thermohaline circulation. Therefore, oceanic mixing at intermediate depth in the eastern tropical Indian intermediate water is modulated by the production rate of the AAIW in the Southern Ocean. Our study provides new evidence for the role that changes in the deep oceanic conditions play in amplifying externally forced climate changes that ultimately lead to drier/moister atmospheric conditions and weaker/stronger monsoons during glacial/interglacial periods over eastern tropical Indian Ocean.