Zn deficiency is the most common micronutrient deficit in rice but also a widespread industrial pollutant. It is unclear how rice responds to Zn depletion or excess, and which signaling molecules link the affected physiological processes. We therefore compared the physiological, transcriptomic and biochemical properties of rice plants subjected to Zn starvation or excess at early and later treatment stages. Both forms of Zn stress inhibited root and shoot growth. Several divalent cations (Fe, Cu, Ca, Mn and Mg) accumulated in Zn-depleted shoots, possibly due to the increased synthesis and activity of promiscuous Zn transporters and chelators. Gene Ontology enrichment analysis of 970 differentially expressed genes revealed overrepresentation of ion and oligopeptide transport, antioxidative defense and secondary metabolism. The expression of genes encoding Fe/Ca-binding peroxidases was activated after 3 days of Zn starvation, boosting the activity of ascorbate peroxidase and thus scavenging H2O2 more effectively to prevent leaf chlorosis. Conversely, excess Zn triggered the expression of genes encoding Mg-binding proteins (OsCPS2/4 and OsKSL4/7) required for antimicrobial diterpenoid biosynthesis. We demonstrated the key components of crosstalk between Zn and other divalent cations under Zn stress conditions, leading to the regulation of gene expression and corresponding biochemical and physiological processes.