Second-generation tricyclic H1 antihistamine loratadine (LTD) has a high permeability, low water solubility, and an oral absorption rate dependent on the rate at which it dissolves in the gastrointestinal tract. One approach suggested for improving the drug’s solubility and rate of dissolution is natural solid dispersion (NSD). The present study evaluated the use of hydrophilic natural polymers, sodium alginate (SA), hyaluronic acid (HA), and xyloglucan (XG), in natural solid dispersion to enhance LTD solubility and dissolution rate. A total of 12 formulations comprising varied drug-to-polymer ratios were produced and analyzed for percentage yield, water solubility, and in vitro dissolution rate. The solubility of LTD was improved in all formulations. Excellent results were achieved with NSD1 (LTD: SA 1:0.25), with a high yield (99%), superior solubility (0.187) compared to pure loratadine (0.0021), and a speedy dissolution rate (98%) within 30 minutes. These studies suggest natural polymers like SA, HA, and XG can considerably increase LTD solubility. When introduced into NSD, these polymers effectively augment LTD dissolving rates, presenting attractive prospects for better bioavailability and therapeutic efficacy.