Plant tissue concepts represent a foundational yet complex domain in secondary biology education, often characterized by persistent conceptual difficulties. This quasi-experimental study evaluated the empirical impact of Guided Inquiry Learning (GIL) on high school students' academic performance in plant tissue topics compared to traditional direct instruction. A total of 48 eleventh-grade students participated, divided equally into an experimental group (n = 24) exposed to GIL and a control group (n = 24) taught via conventional lecture methods. Pretest, posttest, and Hake's normalized gain (N-gain) scores were gathered to assess conceptual growth. Within-group analysis using the Wilcoxon signed-rank test demonstrated statistically significant performance gains for both cohorts (W = 0.000, z = -6.031, p < .001). Descriptive N-gain analysis revealed medium learning gains for both experimental (Mean = 0.455, SD = 0.134) and control groups (Mean = 0.436, SD = 0.063). Diagnostic checks revealed severe violations of parametric assumptions, including non-normality of posttest residuals (Shapiro-Wilk W = 0.935, p = .011) and heteroscedasticity (Levene's F = 13.17, p < .001). Inferential evaluation via Welch's t-test yielded t(29.74) = 1.701, p = .099, Cohen's d = 0.491, while the Mann-Whitney U test indicated U = 350.500, p = .192. Although between-group differences did not achieve formal statistical significance at the alpha = .05 threshold due to limited sample size, the moderate effect size (d = 0.491) highlights substantial practical significance, underscoring GIL's pedagogical potential in enhancing high-level cognitive mastery.