We evaluated potential effects of deltamethrin and fipronil on tiger salamander (Ambystoma mavortium) body mass, behavioral activity, and insecticide tissue residues. Insecticides were applied at realistic concentrations in mesocosms mimicking prairie dog burrows, which are used as refuge by salamanders under natural conditions. Treatments included (1) deltamethrin dust, (2) prairie dog fecal pellets containing fipronil and fipronil sulfone, a metabolite, and (3) controls. Salamanders were monitored before and after treatments, under a before-after-control-impact design. We measured the mass of each individual approximately once per week to assess potential changes in body mass. We used custom-made open-source camera systems to monitor and quantify salamander aboveground activity relative to treatment at ~15 minute intervals; if a salamander was detected outside a burrow at a given point in time, the salamander was classified as active and outside the burrow. On the final day of the experiment, salamanders were euthanized using MS222; whole-body mass was determined, and gonad (ovaries and testes) and liver samples were removed from the carcasses using sterile dissection kits. All tissue was frozen until analysis. Gonad, liver, and whole body samples were assayed for deltamethrin using multiresidue extraction or for fipronil and fipronil sulfone using liquid chromatography with tandem mass spectrometry. This data release consists of four spreadsheets. The first spreadsheet (Fipronil_residues.csv) includes data on treatment (fipronil), sample type (gonads, liver, whole body), fipronil residues measured as nanograms per gram wet weight, and fipronil sulfone residues measured as nanograms per gram wet weight (None Detected = no residues detected). The second spreadsheet (Deltamethrin_residues.csv) includes data on treatment (deltamethrin), sample type (gonads, liver, whole body), and deltamethrin residues measured as nanograms per gram wet weight (None Detected = no residues detected). The third spreadsheet (Body_mass.csv) includes data on salamander identification number, treatment (control, deltamethrin, fipronil), date of body mass measurement, period of experiment (before or after treatment), and salamander body mass in grams. The fourth spreadsheet (Activity.csv) includes camera data on mesocosm identification number, treatment (control, deltamethrin, fipronil), period of experiment (before or after treatment), date of observation, time of observation (using a 24 hour clock), and a binomial variable (1 = yes, 0 = no) for whether or not the associated salamander was detected outside its burrow.