<p><i>Citrus sinensis</i> (L.) Osbeck seedlings were submitted to 0 (HA0) or 0.5 (HA0.5) mM sodium humate and 0.5 (Cu0.5) or 400 (Cu400) µM CuCl₂ for 24 weeks. HA0.5 ameliorated Cu400-induced increases in root concentrations of total phenolics, total flavonoids, nonstructural carbohydrates, and total coumarins, and decreases in root concentrations of total free amino acids (AAs) and total soluble proteins. Similarly, HA0.5 prevented the alterations in root gene expression and metabolite profiles caused by Cu400. The HA0.5-mediated amelioration of Cu400 in roots involved the following factors: (<i>a</i>) less reduction in root growth caused by Cu400 due to less impairment to cell growth, cell wall metabolism, membrane fluidity, and plant hormone signal transduction; (<i>b</i>) less impairment to carbohydrate, energy, and AA metabolisms caused by Cu400 and enhanced capability of roots of Cu400-treated seedlings (RCu400) to maintain plasma membrane fluidity due to lipid remodeling (increased sphingolipids and lysophospholipids and decreased proportion of phospholipids bound by Cu²⁺); (<i>c</i>) less increment in the biosynthesis and accumulation of secondary metabolites in RCu400; and (<i>d</i>) activation of plant hormone signal transduction in RCu400. Roots of HA0-treated seedlings (RHA0) exhibited some adaptive responses to Cu400. For example, Cu400 augmented the biosynthesis and accumulation of some saccharides, organic acids, AAs, lipids (free fatty acids, sphingolipids, and lysophospholipids), alkaloids (melatonin), flavonoids, phenolic acids, and coumarins in RHA0, and upregulated glycolysis/gluconeogenesis, tryptophan metabolism, glutathione metabolism (glutathione S-transferase gene expression), phenylpropanoid biosynthesis, and flavonoid biosynthesis in RHA0.</p>