Conventional dendritic cells (cDCs) play unique roles in immunoregulation and antigen presentation, which is fundamental to protective immunity and are implicated in various autoimmune pathologies. Accordingly, cDCs are targeted in autoimmune and cancer immunotherapies. Recent studies have established key roles of one-carbon cycle metabolism in modulating dendritic cell (DC) fate. PHGDH is central to this pathway, yet its role in DC metabolism remains undefined. We combined integrative omics profiling with functional immunophenotyping and metabolomics analyses to investigate the role of PHGDH in DCs. PHGDH regulates DC effector functions and shapes their intercellular interactions via non-canonical mechanisms. We found that PHGDH-deficient DCs have limited maturation following LPS stimulation and prime weaker effector CD8+ T cells. We found that PHGDH deficiency in DCs rewires crosstalk with neighbor DCs. Our data suggests that PHGDH is involved in intrinsic regulation of redox metabolism and epigenetic rewiring in cDCs, independent of serine biosynthesis. Our data positions PHGDH as a critical immunomodulator of DCs and highlights its potential as a therapeutic target for autoimmune diseases through modulation of DC-mediated immune crosstalk.