Literature shows that production of cottonseed adhesives is feasible to develop an environmentally friendly and competitive bio-based wood adhesive. Defatted cottonseed and water-washed cottonseed meals were prepared from glandless cottonseed and were used in adhesive formulations to produce three-ply yellow poplar (Liriodendron tulipifera) plywood panels as the first objective. These two cottonseed meals were compared with the properties of plywood panels made with an adhesive formulated from a commercial soybean meal, as a control. Adhesive resins were prepared from each protein meal with sodium metabisulfite (Na2S2O5) and one of two polyamido-amine-epichlorohydrin (PAE) wet strength agents, and the plywood panels were produced by hot pressing for 7, 8.5 and 10 minutes at 135°C with a constant pressure of 1.241 MPa. Panels prepared from three protein meals had comparable shear strengths. The combinations of the two cottonseed preparations and the two wet strength agents produced panels with acceptable wet resistant properties, whereas the soybean meal only produced acceptable panels with one of the wet strength agents. Because the panels prepared from the two cottonseed meals had comparable properties, there appears to be no benefit to including a water-washing step to increase the meal’s protein level. The second objective of this research was to reduce the hot press time and develop cottonseed meals into adhesives to become comparable to commercial soybean-based adhesives. New cottonseed, water-washed cottonseed, and commercial in-house soybean meals were separately prepared with deionized water, sodium metabisulfite, and PAE to produce three-ply yellow poplar plywood panels. The panels were hot pressed for 4, 5, and 6 minutes at 135°C with a constant pressure of 1.241 MPa. Panels prepared from the three meals and commercial soybean plywood panels had comparable mechanical shear strengths and water resistance properties. Results indicated that press time, meal types, and interactions were statistically significant. Shear strength results indicate that cottonseed could be used alternatively to soybean. The new cottonseed panels were more resistant to delamination than soybean. The cottonseed meals showed great promise for applicability as a formaldehyde-free, bio-based, and environmentally friendly hardwood plywood wood-based adhesives product for use in interior type applications.